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QP331  .H66  A  microscopical  stud 


RECAP 

A  MICROSCOPICAL  STUDY  OF  CHANGES 


DUE  TO 


Functional  Activity  in  Nerve  Cells. 


BY 


C.    F.    HODGE,    Ph.D. 


Reprinted  from  Journal  of  Morphology,  Vol.  VII.,  No.  2. 


COLUMBIA  UNIVERvSITY 

DEPARTMENT  OF  PHYSIPLOOY 

College  of  Physicians  and  .Suhgeons 
437  west  fifty  ninth  stheet 

NEW   YORK 


BOSTON  : 
GINN    &    CONIPANV. 

1892. 


COLUMBIA    UNIVERSITY 
DEPARTMENT     OF     PHYSIOLOGY 
THE    JOHN    G.   CURTIS    LIBRARY 


Digitized  by  tine  Internet  Arciiive 

in  2010  with  funding  from 

Open  Knowledge  Commons  (for  the  Medical  Heritage  Library  project) 


http://www.archive.org/details/microscopicalstuOOhodg 


A  MICROSCOPICAL  STUDY  OF  CHANGES 


DUE  TO 


Functional  Activity  in  Nerve  Cells. 


BY 


C    F.    HODGE,    Ph.D. 


Reprinted  from  Journal  of  Morphology,  Vol.  Vll..  No.  2. 


BOSTON  : 

GINN    &    COIVlPANY. 

1892. 


TO 

THE   FOUNDER   OF 

THE   MRS.  JONAS  G.  CLARK   FELLOWSHIP   IN    PSYCHOLOGY 

IN   CLARK   UNIVERSITY 

THIS  MEMOIR  IS  RESPECTFULLY  INSCRIBED 

BY  ITS  FIRST  HOLDER 

THE  AUTHOR 


Volume  VII.  November,  i8g2.  Number  2. 


I 


JOURNAL 


OF 


MORPHOLOGY. 


A  MICROSCOPICAL  STUDY  OF  CHANGES   DUE  TO 
FUNCTIONAL   ACTIVITY    IN    NERVE   CELLS. 

C.   F.   HODGE,  Ph.D. 

Experiments  upon  a  series  of  animals,  including  the  frog,  cat,  dog,  birds  (pigeon, 
English  sparrow,  and  swallow),  and  honey  bee,  with  some  observations  upon 
chased  foxes  and  pathological  human  material. 


CONTENTS. 

PACK 

I.  Introductory •        •  95 

II.  Theory  and  Purpose 96 

III.  History  of  Related  Work 98 

IV.  Effects  of  Electrical  Stimulation 114 

V.   Process  of  Recovery  from  Fatigue 130 

VI.  Curves  of  Nerve  Cell  Fatigue  and  Recovery     .        .        .        .138 

VII.  Effects  of  Normal  Daily  Fatigue 143 

VIII.  Conclusions 158 

IX.  Bibliography 160 


I.  Introductory. 

Experiments  for  the  purpose  of  studying  changes  in  the  cells 
of  spinal  ganglia  upon  electrical  stimulation  of  nerves  going  to 
them,  were  begun  in  the  biological  laboratory  of  The  Johns 
Hopkins  University  in  the  winter  of  1887-88,  and  were  there 
continued  through  the  year  1888-89.  During  the  two  succeed- 
ing years  the  work  was  prosecuted  in  the  neurological  labora- 
tory of  Clark  University,     First  of  all,  I  wish  to  express  my 

95 


g6  HODGE.  [Vol.  VII. 

gratitude,  for  his  faithful  supervision  of  the  research  during  the 
whole  time,  to  Dr.  Henry  H.  Donaldson.  Special  thanks  are 
further  due  to  Clark  University,  which  has  provided  me  with 
the  best  obtainable  apparatus  and  afforded  generous  opportu- 
nity for  the  prosecution  of  the  work.  It  is  with  pleasure  also 
that  I  acknowledge  my  indebtedness  to  Professor  H.  Newell 
Martin  and  to  Professor  Warren  P.  Lombard,  for  the  privilege 
of  using  the  apparatus  of  their  respective  laboratories. 

The  research  has  thus  extended  over  a  period  of  nearly  four 
years.  Results  have  been  published  from  time  to  time  in  the 
Americart  Journal  of  Psychology  (23,  24,  25).  Done  from  the 
standpoint  of  the  physiologist  and  morphologist,  rather  than 
from  that  of  the  psychologist,  I  have  not  felt  that  it  would  be 
appropriate  to  give  to  its  publication  in  a  psychological  journal 
the  form  best  suited  to  the  nature  of  the  work.  The  reports 
so  far  have  been  thus  necessarily  incomplete.  I  desire,  there- 
fore, to  give  a  full  resume  of  previous  papers,  thereby  making 
the  following  a  unified  statement  of  the  entire  research  up  to 
date.  This  repetition  is  the  more  allowable,  since,  up  to  this 
point,  the  work  is  a  logical  unit.  The  logical  sequence  from 
the  first  has  been  determined,  not  by  preconceived  notions,  but 
step  by  step  by  the  outcome  of  the  experiments.  Thus,  when 
I  began  by  stimulating  the  sciatic  nerve  of  the  frog,  I  had  little 
enough  idea  that  it  would  bring  me  to  a  study  of  general  ner- 
vous fatigue  and  restoration,  and  to  the  study  of  birds  and  honey 
bees  at  morning  and  at  night.  And  results  still  warrant  further 
prosecution  of  the  work  into  the  investigation  of  the  more  com- 
plex nervous  systems  of  the  higher  animals  and  man  in  conditions 
of  fatigue  and  disease. 

II.   Theory  and  Purpose. 

To  carry  our  knowledge  a  step  farther  into  the  working  of 
the  nerve  cell  is  the  sole  object  of  the  research.  We  already 
know  that  all  the  energy  of  the  animal  body  comes  directly 
from  chemical  changes  which  take  place  in  the  different  tissues. 
The  tissues  have  been  specialized  to  perform  certain  chemical 
reactions,  and  in  the  individual  cells  we  must  find  epitomized 
the  function  of  the  whole  tissue.  That  is  to  say,  did  we  but 
know  all  the  processes  which  take  place  in  a  single  nerve  cell. 


No.  2.]  CHANGES  IN  NERVE   CELLS.  ^j 

we  should  know  or  at  least  have  the  key  to  learn  all  of  nerve 
physiology,  from  the  action  of  the  nervous  mechanism  (?)  in  an 
amoeba's  protoplasm,  through  the  entire  animal  series,  to  the 
activity  of  the  human  brain. 

A  certain  fascination  attaches  to  the  study  of  the  nerve  cell, 
because  it  is  associated  with  the  higher  activities  of  life.  Sensa- 
tion, intelligence,  volition,  are  in  some  way  dependent  upon  the 
integrity  and  healthful  action  of  the  cells  of  the  brain,  and 
many  have  been  the  theories,  without  foundation,  concerning 
the  working  of  the  soul  within  its  "material  sanctuary."  In 
fact,  so  many  ideas,  thoroughly  unscientific  in  character,  have 
appeared  in  this  field,  that  it  is  with  some  slight  danger  that 
one  undertakes  to  work  in  it  even  now.  It  is  still  a  living 
sentiment  that  a  man  who  meddles  much  with  the  brain  is 
seeking  the  "  seat  of  the  soul,"  as  De  Cartes  actually  did,  and 
as  Charles  Bell,  nearly  two  hundred  years  later,  was  accused  of 
doing.  As  a  friend  remarked  to  the  author  on  beginning  the 
work,  "You  will  find  no  changes  in  nerve  cells  corresponding  to 
those  which  take  place  in  a  gland.  Changes  are  demonstrable 
in  gland  cells,  because  these  produce  a  material  secretion  ;  you 
should  find  changes  in  muscle,  because  its  action  results  in 
mechanical  work  ;  but  the  case  of  a  nerve  cell  is  different,  its 
secretion  is  consciousness,  a  thing  outside  the  equation  of  con- 
servation of  physical  energy."  As  he  put  it,  "The  action  of 
nerve  cells  is  in  a  fourth  dimension  of  space."  However,  tran- 
scendental objections  to  the  contrary,  the  problem  is  simple 
enough.  A  nerve  cell  is  certainly  a  minute  speck  of  three 
dimensional,  material  protoplasm.  Compared  with  the  cells  of 
other  tissues  it  is  often  large,  and  compared  with  them,  too,  it 
is  definitely  characterized.  A  nerve  cell  is  in  general  made  up 
of  a  mass  of  granular  protoplasm,  enclosing  a  large  nucleus, 
which  exhibits  a  delicate  reticulation  and  contains  a  prominent 
nucleolus.  In  a  spinal  ganglion  cell,  for  example,  all  these 
characters  are  much  more  prominent  than  in  any  of  the  gland 
cells  wherein  functional  changes  have  been  observed.  If  a 
nerve  going  to  a  gland  be  stimulated,  the  cells  become  active, 
granules  pass  out  of  the  cell  protoplasm  into  the  secretion,  and 
the  cell  nuclei  often  undergo  marked  changes  of  appearance. 
If  a  nerve  going  to  a  ganglion  be  stimulated,  if  the  cells  have 
any  function,  why  might  it  not  be  possible  to  demonstrate  sim- 


^3  HODGE.  [Vol.  VII. 

ilar  changes  in  them  ?  When  changes  in  gland  cells  were 
demonstrated  for  artificial  stimulation,  the  question  arose,  Why 
may  not  similar  changes  occur  in  the  normal  daily  activity  of 
the  gland .''  So  as  changes  due  to  artificial  stimulation  were 
noted  in  nerve  cells,  it  was  realized  that  if  normal,  similar 
changes  should  be  found  in  the  normal  daily  rest  and  activity 
of  the  animal. 

While  so  much  space  in  physiology  is  given  to  processes 
of  digestion  and  nutrition,  very  little  is  given  to  those  distinc- 
tively of  rest.  Indeed,  in  a  leading  physiology  of  the  human 
body  in  this  country,  the  subject  of  sleep  is  not  treated,  and 
even  the  word  "sleep"  does  not  occur,  in  coarse  print,  in  the 
book.  And  yet  what  fact  in  physiology  is  more  clearly  indi- 
cated than  that  of  the  necessity  of  rest  after  activity  ?  An 
animal  is  awake  and  active  for,  we  will  say,  twelve  hours.  It 
then  sleeps  for  twelve  hours.  The  sleeping  and  the  waking  are 
dependent,  without  doubt  in  chief  part,  if  not  entirely,  upon 
processes  which  are  taking  place  in  the  cellular  portions  of  the 
nervous  system.  To  account  for  such  profound  functional 
changes,  is  it  illogical  to  expect  to  find  correspondingly  great 
changes  in  structure  .<*  The  necessity  for  rest  in  a  gland  cell  is 
made  apparent  by  its  loss  of  substance.  If  nerve  cells  do  not 
lose  substance,  or  change  in  some  way,  why  are  we  tired  at 
night } 

III.    History  of  Related  Work. 

A  knowledge  of  cellular  activity  which  will  enable  us  to  appor- 
tion to  each  part  of  the  cell  —  nucleus,  reticulum,  granulation,  etc. 
—  its  peculiar  role,  to  know  the  purpose  for  which  it  exists,  and 
the  work  which  it  does  for  the  common  good,  such  knowledge 
can  only  be  gained  by  study  of  physiological  activity  in  cells, 
and  not  only  in  reproductive  cells,  but  in  cells  of  all  kinds  and 
functions.  It  has  long  been  my  purpose  to  sift  all  the  work 
that  has  ever  been  done  upon  the  line  of  changes  in  cells  due 
to  functional  activity,  and  to  glean  out  whatever  consensus  of 
opinion  may  have  been  reached.  Pressure  of  other  work,  and, 
while  in  Madison,  the  lack  of  all  literature,  either  current  or 
classical,  has  made  it  impossible  to  carry  out  this  plan  as  fully 
as  desired.  A  few  points  require  discussion,  however,  before 
passing  to  a  consideration  of  my  own  experiments. 


No.  2.]  CHANGES  IN  NERVE  CELLS.  99 

There  is,  indeed,  little  enough  consensus.  In  no  field  of  biology 
is  there  such  a  Babel  of  discord,  and  the  reason  for  this  is 
obvious.  The  material  of  observation  here  is  not  permanent 
form,  but  flitting,  vanishing,  ever-changing  phases  of  action. 
What  one  observer  sees  is  gone  before  another  observer  can 
confirm  it.  Further  than  this,  and  aside  from  the  difficulty  of 
making  exact  observations,  the  causes  which  modify  or  influ- 
ence cellular  activity  are  little  understood.  Hence  causes  which 
might  account  for  difference  in  results  are  likely  to  be  over- 
looked, and  results  themselves  are  claimed  to  be  different ;  con- 
siderations like  the  above  will  be  of  assistance  as  we  proceed. 

What  Minot  (52,  p.  98)  would  say  of  the  whole  organism  is 
true  of  its  individual  cells.  No  process  is  more  characteristic 
of  living  protoplasm  than  growth.  And  growth  in  a  metazoan 
may  be  due  to  either  cell-multiplication  or  to  cell-growth.  The 
first  is  plainly  reproduction.  May  not  also  cell-growth  (57,  p.  23  ; 
51,  p.  439)  be  considered  in  essential  nature,  a  process  of  the 
same  kind,  in  which  the  increment  of  matter  gained  is  used 
for  some  other  purpose  by  the  cell  than  that  of  reproducing 
another  cell  like  itself .-'  An  amoeba,  or  a  tissue-cell,  grows  and 
then  divides  into  two  cells,  we  will  say,  of  exactly  the  same 
kind,  and  half  the  size  of  the  original.  A  working  tissue-cell 
grows  to  twice  normal  size,  but,  instead  of  dividing,  it  now 
throws  off  half  of  its  substance,  let  us  say,  in  the  form  of  zymo- 
gen granules.  That  is  to  say,  the  cell  has  become  specialized, 
so  that  instead  of  dividing  into  two  equivalent  parts  it  divides 
into  two  unequal  parts ;  the  one  remaining  as  the  original  cell, 
the  other  passing  off  to  do  the  work  for  which  the  cell  has 
become  specialized  to  perform.  If  there  is  any  truth  in  this 
view,  we  should  expect  to  find  the  same  mechanisms  which 
mediate  cell-reproduction  active  in  cell-function.  Exactly  what 
the  reproductive  mechanisms  of  a  cell  are,  despite  the  vast 
amount  of  work  devoted  to  the  subject,  is  still  a  matter  of  con- 
troversy. I  shall  attempt  no  special  discussion,  and  hence  shall 
refer  to  but  two  or  three  papers  which  bring  out  points  of  imme- 
diate use  to  us,  bearing  upon  the  general  subject  of  cellular 
activity. 

In  the  process  of  division  no  part  of  the  cell  is  likely  to  show 
such  active  changes  as  the  nucleus.  In  fact,  the  nucleus  is  not 
infrequently  called  the  reproductive  organ  of  the  cell.     May  not 


lOO 


HODGE.  [Vol.  VII. 


the  nucleus  be  equally  active  in  the  growth  of  protoplasm  for 
use  in  functional  activity,  as  well  as  for  cell-division  ? 

An  experiment  of  Boveri  (7)  in  confirmation  of  observations 
by  the  Hertwigs  (22)  throws  some  light  upon  functions  of 
the  nucleus.  The  experiment  consists  in  fertilizing  a  denu- 
cleated  fragment  of  a  sea-urchin's  &%%  with  a  spermatozoan  of 
another  species ;  Rauber's  (70)  experiment,  upon  toads'  and 
frogs'  eggs,  repeated  upon  a  form  where  success  was  pos- 
sible. Rauber  wished  to  ascertain  the  relative  influence  of 
nucleus  and  protoplasm  in  the  determination  of  species.  Boveri 
carried  the  experiment  far  enough  to  demonstrate  that  such 
denucleated  fragments  developed  into  pure  male-type  embryos. 
That  is,  the  female  protoplasm  had  no  influence.  It  served 
simply  as  food  matrix  in  which  the  male  nucleus  could  develop. 
If  a  female  nucleus  is  present  in  the  fertilized  fragment,  a  hybrid 
is  developed.  So  that  Boveri  is  confident  in  concluding  that 
the  nucleus  alone  carries  specific  characters  from  parent  to  o£E- 
spring.  Watase  (83,  p.  262),  who  gives-  great  prominence  to 
the  part  taken  in  cell-division  by  a  portion  of  the  protoplasm 
(archoplastic  spheres  and  filaments),  coincides  with  the  above 
opinion  in  the  following  words  :  "  It  is  now  quite  generally  con- 
ceded that  the  nucleus  of  the  fertilized  ovum  contains  all  the 
hereditary  characteristics  of  the  parent  organisms." 

If,  then,  a  single  microscopical  nucleus  is  capable  of  deter- 
mining the  form,  nuclei,  and  protoplasm  of  all  the  cells  of  an 
animal,  a  fortiori,  the  nucleus  should  certainly  determine  the 
protoplasm  of  its  own  cell.  The  truth  of  this  is  seen  in  the 
development  of  any  tissue  (53,  p.  17).  At  first  there  is  a  mass 
of  nuclei  with  scarcely  a  trace  of  protoplasm  ;  then  around  each 
nucleus  protoplasm  is  gradually  laid,  until,  in  form,  amount,  and 
structure,  the  adult  cell  is  attained.  Whence  comes  this  proto- 
plasm, if  it  is  not  developed  from  the  nuclei .-'  What  are  nuclei 
doing  in  solid  heaps  unless  busy  making  protoplasm  ?  From 
the  role  which  they  play  in  a  developing  ovum,  it  is  plain 
that  nuclei  are  things  too  vital  and  active  to  be  Iving  around 
idle. 

This  brings  us  to  a  principle  which  should  underlie  all  study 
of  cellular  activity.     It  may  be  stated  in  two  ways. 

(i)  In  any  specialised  tissue,  seek  for  changes  due  to  functional 
activity  in  the  structures  most  prominent  in  the  cells  of  that  tissue. 


No.  2.]  CHANGES  IN  NERVE  CELLS. 


lOI 


(2)  Conversely,  a  cell  becomes  specialized  to  perform  a  certain 
function  only  by  an  increased  growth  of  certain  of  its  parts. 

Thus  reproductive  tissue  is  most  richly  nucleated.  Possibly- 
even  more  richly  nucleated  is  cellular  nerve  tissue.  In  gland 
tissue,  nuclei  are  quite  prominent ;  but  the  characteristic  of  a 
gland  cell  is  its  granulation.  From  a  red  blood  corpuscle  the  nu- 
cleus may  be  entirely  lacking ;  the  reticulum,  stroma,  is  scarcely 
discernible ;  all  that  is  left  is  a  highly  specialized  protoplasm ; 
and  here  the  only  change  we  know  is  that  from  reduced  to  oxy- 
haemoglobin,  and  vice  versa.  Intermediate  between  the  last  two 
stand  such  mechanical  tissues  as  cartilage,  bone,  connective  tis- 
sues, and,  we  must  add,  nerve  fibres  and  muscle.  These,  when 
adult,  consist  chiefly  either  of  comparatively  inert  intercellular 
substance,  or  of  what  we  may  consider  a  special  development 
of  a  fibrillar  cell-reticulum.  And,  aside  from  mere  changes  in 
form,  muscular  contraction,  reticular  contraction  as  seen  in 
amoeba  and  ciliated  epithelium,  etc.,  and  possibly  the  changes 
in  archoplastic  spheres  and  filaments,  where  do  we  find  changes 
in  the  reticulum  of  cells  .-* 

In  running  through  the  list  of  tissues,  therefore,  to  ascertain 
what  changes  connected  with  functional  activity  have  been  ob- 
served in  each,  we  shall  watch  for  the  following  points  :  — 

1.  Changes  in  nucleus. 

2.  Changes  in  protoplasm  \  ""•  Granulation. 

)  b.  Reticulation. 

I  question  the  advisibility  of  further  refinement  at  present. ^ 

^  It  is  immaterial  to  my  present  purpose,  although  it  may  not  be  to  a  future  one, 
whether  we  consider  the  structure  of  protoplasm  to  conform  to  any  of  the  views 
advanced  since  the  "  structureless  slime  "  of  Dujardin  and  Von  Mohl.  Protoplasm 
must  be  something  more  than  this.  Lymph  is  constantly  soaking  through  it,  and 
plus  this  are  certainly  granules  of  some  sort  and  a  fibrillar  meshwork  of  some  kind. 
In  this  research  I  am  not  using  sufficiently  high  powers,  or  sufficiently  special  methods, 
to  make  it  a  matter  of  importance  whether  protoplasm  is  the  zoogloea  of  special 
bacteria  of  Altmann,  or  the  foam  of  Butschli.  I  therefore  adhere  to  the  old  familiar 
view  of  Brucke,  Arnold,  and  Max  Schultze. 

With  regard  to  the  nucleus,  the  writer  has  often  wished  that  he  had  applied 
methods  which  would  have  enabled  him  to  follow  the  substance,  chromatin,  a  little 
more  closely.  This  might  have  been  possible  as  it  was,  had  there  not  been  so  many 
dififerent  kinds  of  safranin  in  the  market,  with  the  exception  of  one  sample,  none  of 
which  stained  chromatin  properly.  This  may  be  remedied  in  future,  and  the  matter 
does  not  concern  us  vitally  at  present 


J02  HODGE.  [Vol.  VII. 

Reproductive  Tissues. 

No  description  of  the  formation  of  spermatozoa  is  necessary. 
Views  as  to  details  differ  among  different  authorities  (39,  p.  900 ; 
ej,  p.  688  ;  22,  p.  17) ;  but  all  are  agreed  as  regards  nearly 
everything  that  touches  our  point  of  view.  In  general,  the 
nucleus  is  transformed  into  the  head  and  the  protoplasmic  re- 
ticulum develops  into  a  vibratile  flagellum.  The  head  assumes 
peculiar  forms  in  different  types,  but  whether  it  shows  any 
increase  or  decrease  in  size  I  am  unable  to  say.  Processes  of 
division  have  recently  been  observed,  in  which  a  portion  of  the 
head  is  extruded  after  the  fashion  of  polar  bodies  (5). 

The  ovum  also  presents  features  of  interest.  Here  both 
nucleus  and  protoplasm  increase  in  size,  often  at  the  expense 
of  surrounding  cells  (18,  pp.  5  ff.),  the  nucleus  in  maturation  suf- 
fering a  reduction  to  one-fourth  its  chromatin  by  extrusion  of 
polar  bodies  (63).  Besides  changes  in  nucleus  and  food  material 
the  reticulum  often  assumes  a  peculiar  structure,  to  form  the 
"zona  radiata"  around  the  outside  of  the  ovum. 

It  may  be  well  to  bear  in  mind  all  phases  of  protoplasmic  and 
nuclear  activity  passing  by  the  names  of  ookinesis,  cytokinesis, 
or  karyokinesis.  Let  us  see  if  anything  in  the  functional  ac- 
tivity of  other  tissues  may  be  found  to  resemble  these  processes, 
or  those  of  direct  nuclear  division. 

Gland. 

Of  importance  in  their  influence  upon  theories  of  secretion 
were  the  first  experiments  of  Heidenhain.  Secretion  could  no 
longer  be  thought  of  as  the  "straining  off"  of  Malpighi  (47, 
I,  p.  464),  or  the  "  diffusion  stream  "  of  Deutroschet,  when  the 
activity  of  the  cells  themselves  had  once  been  demonstrated. 
Heidenhain  (19,  20,  21)  found  that,  as  the  cells  secreted,  their 
appearance  changed  in  a  marked  degree.  In  general,  a  granular 
zone  next  the  lumen  disappeared,  leaving  the  cells  shrunken. 
The  nucleus  in  the  meantime,  from  being  small  and  irregular  in 
outline,  became  swollen.  Protoplasm  grew  again,  and  from  its 
substance  arose  a  new  zone  of  granules.  Sooner  or  later  the 
secreting  cells  go  to  the  ground  and  new  cells  spring  up  to  take 
their  places. 


No.  2.]  CHANGES  IN  NERVE  CELLS.  103 

The  evidence  for  this  last  point  is,  however,  questioned  by 
Langley,  who  strongly  advocates  the  opposite  view,  that  after 
secretion,  and  in  fact  during  secretion,  the  same  cells  refill  with 
protoplasm  and  zymogen  granules,  and  so  on  indefinitely.  The 
facts  thought  by  Heidenhain  to  indicate  cell-renewal  are  given 
another  interpretation  by  Langley  (34,  p.  6^6).  He  also  ques- 
tions whether  the  nucleus  actually  swells,  and  maintains  that  it 
simply  appears  larger  in  proportion  to  the  greatly  shrunken 
cells.  In  the  same  paper  (p.  698)  Langley  emphasizes  another 
point  of  great  importance  to  us,  viz.  that  processes  of  rest  and 
activity,  anabolism  and  katabolism,  go  on  in  the  same  cells  at  the 
same  time.  Hence  the  appearance  of  a  cell  at  any  time  depends 
upon  whether  one  or  the  other,process  is  in  ascendency.  This 
may  account  for  the  fact  that  one  observer  (62)  has  found  that 
the  cells  of  the  gastric  glands  in  the  frog  increase  in  size  for 
twelve  to  eighteen  hours  after  feeding,  and  then  gradually 
resume  their  normal  size.  This  observation,  however,  stands 
alone,  and  during  his  twelve  years  of  close  study  Langley  has 
seen  nothing  to  confirm  it.  In  general,  Langley  makes  little  of 
changes  of  the  nucleus. 

Seiller  (76),  in  a  special  study  of  mucous  cells,  by  most 
recent  methods,  supports  the  view  of  Langley,  that  goblet  cells 
do  not  perish  in  secretion,  but  regenerate  their  protoplasm. 

Great  prominence  is  given  to  the  action  of  the  nucleus  by 
Ogata  (60)  in  his  work  upon  pancreas  secretion.  A  body  with 
peculiar  staining  properties,  plasmasoma,  arises  in  the  nucleus, 
and  migrating  out  into  the  protoplasm  may  give  rise  to  a  mass 
of  zymogen  granules ;  or  it  may  develop  into  a  new  nucleus, 
form  a  new  cell  about  it,  and  then  produce  zymogen  gran- 
ules. That  is,  the  process  is  chiefly  reproductive  in  character. 
There  may  be  a  stable  mechanism  in  the  cells  which  can  manu- 
facture zymogen  granules,  but  under  special  stimulation  this  is 
not  sufficient  (p.  430).  Here,  moreover,  the  reproductive  proc- 
ess is  different  from  ordinary  cell-division,  in  which  both  cells 
live ;  the  old  cells  in  this  case  dying  away.  It  is  different  also 
from  the  fact  that  there  is  nothing  comparable  with  karyo- 
kinesis  ;  nor  does  the  formation  and  migration  of  plasmasoma 
resemble  direct  nuclear  division.  Kiihne  and  Lea  (33)  saw 
granules  in  living  cells  of  triton's  pancreas  streaming  from  the 
neighborhood  of  the  nucleus  toward  the  lumen   (21,  p.   203); 


I04 


HODGE.  [Vol.  VII. 


and,  in  addition  to  this,  Ogata  (60,  p.  432)  observed  them  in 
the  act  of  passing  out  of  the  nucleus.  Platner  (64)  does  not 
confirm  Ogata's  observations ;  finding  instead  frequent  cases 
of  nuclear  budding  (Kernsprossung)  after  good  feeding.  His 
method,  however,  being  so  different  from  that  of  Ogata,  renders 
minute  comparison  of  results  impossible. 

An  additional  point  of  interest  in  pancreas  secretion  is  made 
by  Oppel  (61)  ;  viz.  that  the  nucleus  from  being  clear  and  retic- 
ular in  the  resting  condition  shrinks  and  comes  to  take  a 
dense  homogeneous  stain  after  secretion.  Other  changes  in  the 
cells  are  Uke  those  already  described. 

Van  Gehiichten  (14,  15),  on  the  other  hand,  is  strongly  opposed 
to  the  view  that  the  nucleus  suffers  any  change  during  secre- 
tion. In  case  of  the  digestive  cells  of  Ptychoptera  larva,  which 
he  studied,  it  is  in  fact  often  thrown  out  with  the  secretion.  In 
this  case  the  cell  dies,  so  that  he  concludes  that  the  nucleus  is 
essential  to  cell  life,  but  not  to  secretion.  How  the  cells  are 
renewed  is  not  observed ;  but  nothing  like  cell-division  is  pres- 
ent. It  is  a  little  strange  that,  while  Van  Gehiichten  argues 
against  any  change  in  the  nucleus,  he  figures,  side  by  side,  in 
apparently  similar  cells,  nuclei  of  most  diverse  sizes,  some  nuclei 
being  easily  twice  the  diameter  of  others. 

Something  similar  takes  place  in  mammary  glands  ;  but  here 
the  nuclei  actively  divide,  and  a  part  passes  out  into  the  secre- 
tion. No  exact  measurements  exist,  to  my  knowledge,  but 
reference  to  the  figures  usually  given  (^y,  p.  723  ;  39,  p.  391  ; 
21,  p.  383)  reveals  the  fact  that  the  nuclei  are  out  of  all  pro- 
portion larger  in  the  active  than  in  the  resting  gland.  Here, 
then,  would  seem  to  be  found  a  correlation  between  size  of 
nucleus  and  secreting  activity  of  cell.  If  these  nuclei  did  not 
increase  in  size.  Van  Gehiichten's  statement,  that  nuclei  have 
nothing  to  do  with  secretion,  might  have  a  more  general  applica- 
tion. The  secreting  cells  in  case  of  mammary  glands  show  also 
great  variations  in  amount  and  constitution  of  protoplasmic  con- 
tents during  the  different  phases  of  rest  and  activity. 

For  the  cells  of  the  liver  both  Heidenhain  (21,  p.  222)  and 
Langley  (35)  describe  a  marked  set  of  changes  in  the  pro- 
toplasm, similar  in  the  main  to  the  changes  in  other  glands. 
Heidenhain  (21,  p.  224)  says  that  the  nucleus  is  variable  in 
appearance,  but  does  not  go  into  detail. 


No.  2.]  CHANGES  IN  NERVE   CELLS.  105 

Secular  changes  in  liver  cells  of  frogs  have  been  studied 
with  great  care  by  Alice  Leonard  (41).  The  cells  are  found 
to  vary  greatly  in  size  at  different  seasons,  reaching  a  maxi- 
mum in  November,  and  shrinking  to  less  than  one-fifth  this 
size  by  April.  The  nucleus,  on  the  contrary,  is  smallest  in 
November,  6  /x  in  diameter,  and  largest,  ^.6  fi,  in  April.  The 
protoplasm  may  be  said  almost  to  disappear  during  the  winter, 
pigment  in  the  cells  showing  an  increase  in  amount  at  the  same 
time.  By  this  extreme  change,  an  action  of  different  stains 
upon  constituents  of  the  cell-protoplasm  is  brought  to  light  ; 
viz.  that  eosin  (41,  p.  34)  stains  carbohydrate,  and  nigrosin 
albuminous  material. 

There  is  seen  to  be  little  agreement  as  to  the  action  of  gland 
cells,  and  more  can  scarcely  be  expected  as  to  results  until 
methods  become  better  known,  more  precise,  and  more  con- 
sensus as  to  their  use  is  reached.  So  far  little  more  can  be 
said  to  be  established  than  that  during  rest  the  cells  become 
filled  with  granules,  and  that  during  secretion  these  granules 
pass  out,  generally  leaving  the  cell  shrunken.  A  few  obser\^a- 
tions  indicate  a  probability  that  these  granules  arise  in  the 
nucleus.  One  writer  (60)  affirms  the  fact.  The  fact  that  nuclei 
are  sometimes  extruded  during  active  secretion,  as  occurs  in 
mammary  glands  and  those  of  the  digestive  tract  in  insects 
(Van  Gehiichten),  is  not  necessarily  opposed  to  this  view. 
Whether  the  nucleus  swells,  or  shrinks,  or  changes  in  staining 
properties  is  a  question  of  dispute.^ 

Muscle. 

"A  simplified  view  of  the  histology  of  the  striped  muscle 
fibre"  advanced  by  Melland  (49)  in  1885  is  the  one  adopted  in 
the  following  discussion.  According  to  this  we  have  to  deal 
with  a  highly  specialized  cell-reticulum  with  fibrils  arranged  in 
cross  and  longitudinal  series.  This  is  supposedly  the  contrac- 
tile mechanism.  Between  the  meshes  of  this  reticulum  is  a 
structureless,  semifluid  muscle  plasma.  Scattered  through  the 
muscle  substance  or  lying  just  underneath  the  sarcolemma  are 

'  From  the  first  the  writer  has  intended  to  repeat  the  more  important  experiments 
in  this  field  of  gland  histology,  anrl  until  an  opportunity  for  doing  so  presents  itselt 
further  discussion  of  the  subject  will  hardly  be  profitable. 


Io6  HODGE.  [Vol.  VII. 

inconspicuous  (for  adult  muscle)  nuclei,  embedded  in  a  little 
granular  protoplasm. 

Before  proceeding  it  may  be  well  to  ask  in  which  one  of  the 
above  elements  we  should  expect  to  find  changes  due  to  meta- 
bolic processes.  From  the  axioms  with  which  we  started  out, 
the  reticulum  being  the  characteristic  feature  of  the  tissue,  if 
any  change  occurs  it  should  occur  here.  We  should  certainly 
not  expect  to  find  any  change  in  the  nuclei.  For,  aside  from 
their  insignificant  size,  the  nucleus  has  never  been  found  to  take 
any  part  in  the  function  of  contractility. 

Any  change,  then,  must  be  sought  in  fibrillar  or  interfibril- 
lar  substance.  From  the  physiological  fact,  that  little  or  no 
increased  nitrogenous  waste  occurs  from  increased  muscular 
work,  we  reason  to  a  comparatively  stable  contractile  mechan- 
ism in  muscle,  comparable  to  the  iron-work  of  a  steam-engine. 
We  could  hardly  expect  to  find  any  change  in  a  mechanism  of 
this  sort  from  a  single  day's  work.  We  are  therefore  confined 
to  the  interfibrillar  plasma,  and  here  we  undoubtedly  have  active 
metabolic  changes ;  but  the  lack  of  definite  granulation  must 
add  greatly  to  the  difficulty  of  demonstrating  visually  any  proc- 
esses which  may  take  place. 

As  might  be  expected,  muscle  tissue  has  been  worked  along 
this  line  with  little  success. 

Du  Bois-Reymond  (ii,  pp.  11-72)  discovered,  as  he  at  first 
supposed,  marked  changes  due  to  fatigue.  These  consisted  in 
the  breaking  up  of  the  muscle  substance  into  irregular  lumps  ; 
or,  with  entire  loss  of  fibrillar  structure,  into  fine  granules.  On 
further  experiment,  however,  he  found  that  the  phenomenon 
could  be  produced  by  simple  stretching  of  the  muscle.  It 
occurred  in  equal  amount  whether  the  muscle  was  stretched, 
or  stretched  and  stimulated.  So  that  he  concludes  by  saying 
(11,  p.  72)  "that  frogs'  muscles  which  were  stimulated  to  com- 
plete exhaustion,  as  far  as  the  appearance  of  their  primitive 
fibres  goes,  are  the  same  as  muscles  which  have  not  been 
stimulated." 

Again,  Roth  (72),  in  a  most  heroic  series  of  experiments  in 
which  muscles  of  frogs  and  rabbits  were  stimulated  in  situ  con- 
tinuously for  five,  ten,  and  even  twenty  days,  succeeded  in 
demonstrating  chiefly  such  changes  as  occur  in  pathological 
degeneration  of  muscle.     The  muscle  substance  became  vacuo- 


No.  2.]  CHANGES  IN  NERVE  CELLS.  107 

lated  in  some  cases,  in  others  not  ;  was  broken  up  into  lumps 
and  granules  which  had  lost  fibrillar  structure  in  part  or  alto- 
gether, and  showed  waxy  degeneration.  Some  fibres  exhibited 
the  discoidal  breaking  up  of  muscle  substance  commonly  seen 
in  typhoid  fever.  That  is,  the  mechanism  was  broken,  not 
exhausted.  The  muscle  nuclei  showed  no*  change  whatever. 
Possibly  the  vacuolation  which  appears  in  some  instances  may 
be  reckoned  as  genuine  fatigue  effect. 

Under  this  head  I  may  call  attention  to  a  few  points  in  the 
metabolism  of  another  mesoblastic  tissue  ;  viz.  the  blood. 

Alice  Leonard  (41,  p.  39)  points  out  the  fact  that  the  blood  is 
greater  in  amount  in  November  than  at  any  other  season,  and 
the  red  corpuscles  stain  bright  red  with  eosin  at  this  time. 
During  the  winter  they  take  the  stain  less  and  less,  become 
smaller,  until  the  minimum  is  reached  in  May.  By  July  they 
begin  to  enlarge  again  and  to  take  the  stain.  The  nuclei,  more- 
over, stain  differently  at  different  seasons  and  are  found  to  dif- 
fer both  in  structure  and  form,  staining  in  some  corpuscles 
densely,  in  others  showing  the  usual  reticulum.  They  may  also 
appear  shrunken  and  irregular  or  oval  and  clear. 

Something  similar  for  mammalian  corpuscles  while  still  nu- 
cleated is  pointed  out  by  Howell  (26).  Immature  erythroblasts 
are  nucleated  red  corpuscles  having  a  large  reticulate  nucleus  and 
a  small  amount  of  haemoglobin.  These  divide  by  karyokinesis  for 
several  generations  until  finally  a  form  is  reached,  the  mature 
erythroblast,  having  a  smaller  densely  stained  nucleus  and  large 
amount  of  haemoglobin.  When  the  nucleus  has  lost  its  reticu- 
lum, no  further  division  is  possible,  and  it  is  then  extruded  from 
the  corpuscle  to  be  dissolved  in  the  plasma. 

Nei've   Tissue. 

All  nerve  cells  are  phylogenetically  cells  of  the  epiblast.  In 
any  section  of  skin,  from  the  deepest  layer  of  columnar  cells  to 
the  horny  scales  at  the  surface,  we  may  observe  a  series  of 
changes  which  have  a  deep  physiological  significance.  Here  we 
have  at  a  glance  the  life  history  of  an  epithelial  cell.  Is  it  the 
story  of  a  cell  being  born,  growing  to  maturity,  and  dying  of  old 
age  ?  It  may  be  so.  Or  is  it  the  case  of  a  cell  being  crowded 
away  from  its  supply  of  nourishment  and  dying  of  starvation  } 


I08  HODGE.  [Vol.  VII. 

This  also  may  be  true.  Is  it  the  case  of  a  cell  doing  its  work, 
and,  under  the  hail  of  changes  which  the  external  world  showers 
upon  it,  dying  of  fatigue  t  And  this  may  be  true.  So  that  we 
have  epitomized  in  a  single  row  of  cells  three  great  problems  of 
life  :  its  period  of  duration,  struggle  for  existence,  and  fatigue. 

No  series  of  changes  anywhere  in  the  body  have  a  more 
direct  bearing  upon  changes  during  the  life  history  of  a  nerve 
cell  than  this  series  in  a  cell  of  the  epidermis.  The  cells  begin 
life  with  a  large  nucleus  and  little  protoplasm  exactly  as  a  nerve 
cell  does.  Protoplasm  grows  much,  nucleus  grows  somewhat, 
like  a  developing  ganglion  cell.  Farther  on,  the  nucleus  begins 
to  shrink,  looses  its  reticular  structure,  and  disappears  when  the 
change  of  the  cell  from  protoplasm  to  horn  has  been  completed, 
A  similar  set  of  changes  have  been  described  for  the  atrophy  of 
nerve  cells,  the  end  product  of  course  being  different  in  the  two 
cases.  And  whether  the  life  history  of  nerve  and  epithelial  cells 
is  comparable  to  the  end  remains  to  be  seen  when  the  changes 
due  to  aging  have  been  fully  worked  out  for  the  nerve  cell. 
We  clearly  have  in  the  epidermis  functional  activity  involving 
the  destruction  of  cells.  This  fact  finds  a  natural  explanation 
in  the  superficial  position  of  the  cells.  Why  this  should  not  be 
the  case  with  nerve  cells  will  be  discussed  later. 

A  single  case  of  marked  changes  in  epidermal  cells  due  to 
artificial  stimulation  is  given  us  by  Kodis  (28)  for  the  tadpole. 
Kodis  finds  that  one  hour's  electrical  stimulation  of  the  skin 
occasions  a  shrinkage  in  the  epidermal  nuclei  of  nearly  sixty  per 
cent  (figuring  volume  of  nuclei  from  measurements  taken  from 
Kodis'  drawings)  (compare  Taf.  Ill,  Fig.  34  with  Taf.  I,  Fig.  i). 
The  nucleus  at  the  same  time  becomes  granular  and  dark.  The 
nucleolus  also  shrinks  and  ceases  to  stain  bright  red  with  safra- 
nin  as  it  does  in  the  resting  cells.  With  the  exception  of  this 
last,  which  is  not  so  clearly  demonstrated  in  my  specimens,  the 
changes  are  quite  similar  to  those  taking  place  upon  stimulating 
the  nerve  of  a  spinal  ganglion. 

We  shall  enter  now  the  vast  field  of  nerve  literature  with  an 
eye  single  to  the  subject  in  hand  ;  viz.  microscopical  changes 
connected  with  functional  activity.  Only  so  much  of  morpho- 
logical interest  will  be  cited  as  is  necessary  to  supply  a  physical 
basis  for  physiological  action.  In  brief,  the  conception  of  the 
minute  structure  of  nerve  elements  which  has  satisfied  every 


No.  2.]  CHANGES  IN  NERVE   CELLS.  109 

condition  of  my  research  is  that  furnished  us  by  Max  Schultze 
(75)  and  confirmed  later  by  the  work  of  Kupffer  (31),  Boveri  (6), 
and  Joseph  (27).  My  preparations  do  not  in  any  way  support 
the  tubular  theory  which  Nansen  (56)  has  drawn  from  his  obser- 
vations upon  the  nerves  of  invertebrates.  This  conception  is 
that  the  axis  cylinder  consists  of  a  bundle  of  fine  fibrils  floating 
in  a  plasma.  All  fibrils  arise  as  outgrowths  of  nerve  cells  (29, 
p.  51),  and  are  seen  continued  into  the  cell  as  the  fibrillar  reticu- 
lum of  the  cell-protoplasm.  In  the  cell,  and  to  some  extent  in 
the  nerve  fibre,  granules  occur  between  the  fibrils.  Those  in 
the  fibre  are  exceedingly  fine,  in  the  cell  are  generally  coarse 
and  so  densely  packed  as  to  hide  the  reticulum  altogether.  We 
have  thus  at  least  the  two  things  necessary  for  a  nerve  mechan- 
ism :  the  fibril  to  conduct,  and,  in  close  touch  with  this,  a  gran- 
ular substance,  changes  in  which  may  serve  to  originate  or 
modify  the  nerve  impulse.  In  addition  we  have  a  nucleus  and 
nucleolus,  proportionally  as  large  or  larger  than  the  nucleus  of 
a  growing  ovum.  Thus  all  the  elements  of  cell  structure, 
nucleus,  granulation,  reticulum,  are  highly  developed  in  the 
ganglion  cell.  May  we  not  then  expect  to  find  changes  like 
those  of  an  ovum  in  the  nucleus,  and  changes  in  the  granular 
contents  like  those  occurring  in  gland  cells  t  We  have  no 
ground  to  expect  to  find  any  change  in  the  fibrillae  themselves. 

A  good  deal  of  work  has  been  misdirected  to  the  study  of 
so-called  pathological  changes  in  nerve  cells.  I  say  misdirected, 
because  until  normal  processes  are  known  it  is  clearly  impos- 
sible to  draw  the  line  between  what  is  normal  and  what  is 
abnormal. 

A  careful  statement  of  pathological  changes  is  given  by  Ober- 
steiner  (59,  pp.  112-116  and  125-129).  The  gross  process  of 
degeneration  in  a  nerve  fibre  is  comparatively  simple  and  too 
well  known  to  require  description.  For  the  ganglion  cell  patho- 
logical changes  are  exceedingly  varied.  Of  the  nine  varieties 
described  by  Obersteiner  I  shall  at  present  file  a  word  of  caution 
against  two.  Simple  atrophy,  he  says,  begins  by  shrinkage  with 
loss  of  structure  of  the  nucleus,  its  outline  becoming  jagged, 
followed  by  shrinkage  of  cell,  disorganization  of  processes,  and 
finally  ending,  it  may  be,  in  the  disappearance  of  the  entire 
neuron.  Again,  vacuolation  is  given  as  a  pathological  change 
in  cases  of  inflammation.     Although  Obersteiner  is  careful  to 


no 


HODGE.  [Vol.  VII. 


State  that  the  amount  of  vacuolation  must  be  considerable  and 
its  presence  in  the  cells  general,  if  we  are  to  consider  it  a  sign 
of  pathological  change,  still  I  doubt  if  pathologists  realize  the 
amount  of  shrinkage  and  vacuolation  which  may  occur  in  normal 
fatigue.  As  to  the  other  forms,  fatty  or  pigmentary  degenera- 
tion of  chronic  atrophy  in  paralytics  and  drunkards,  sclerosis, 
the  calcification  oi  plaques  JauneSy  etc.,  fragmentation  of  nuclei, 
etc.,  there  is  no  doubt  as  to  their  pathological  nature. 

For  the  spinal  ganglia  Angelucci  (4)  in  cases  of  chronic  and 
acute  myelitis  and  paralytic  insanity  describes  among  other 
changes  a  shrinking  up  of  the  nucleus,  its  outline  becoming 
"  Stelliforme,"  and  finally  it  disappears.  Similar  appearances 
are  found  by  Miiller  (55,  PI.  I,  Fig.  7)  in  normal  ganglia  and 
described  without  explanation  as  degenerated  nuclei.  Rosen- 
bach  (68)  obtained  about  the  same  results,  shrinkage  and  dis- 
appearance of  nucleus  with  vacuolation  of  protoplasm,  from  the 
spinal  ganglia  of  dogs  which  had  been  starved.  And  Lewen 
(42)  finds  the  same  appearances  in  the  ganglion  of  the  vagus 
nerve  in  consumption  and  exhausting  disease  of  heart  and 
stomach.  He  attributes  them  to  deficient  nutrition.  R.  Schulz 
(74)  from  examination  of  twenty  cases  draws  the  generalization 
that  pigment  increases  in  the  ganglion  cells  of  the  spinal  cord 
with  age  and  impaired  nutrition.  Whitwell  (84)  describes  vacu- 
olation in  the  nucleus  of  both  large  and  small  pyramidal  cells 
of  the  cortex  in  cases  of  dementia,  especially  when  following 
epilepsy.  Mamurowski  (50)  describes  a  case  of  death  from  pro- 
gressive paralysis  due  to  alcoholism,  in  which  the  peripheral 
nerves  showed  degeneration,  but  no  change  was  observable  in 
either  brain  or  spinal  cord.  The  above  represents  but  a  few  of 
the  observed  changes  which  might  be  sifted  out  of  the  literature 
of  the  subject. 

In  the  line  of  experimental  pathology,  beside  the  experiments 
just  referred  to,  Rosenbach  (69)  has  found  degeneration  of 
fibres  and  atrophy  of  ganglion  cells  in  the  cord  of  dogs  in  the 
neighborhood  of  compression.  In  fact,  the  Russians  have  done 
considerable  work  of  this  kind,  and  from  the  title  of  several 
of  their  papers,  I  had  expected  to  find  the  subject  of  normal 
fatigue  treated.  I  was,  however,  fortunate  enough  to  obtain  a 
reading  of  the  more  important  articles,  and  found  them,  in 
purpose   and   idea,  pathological.      For   example,  Anfimow    (i) 


No.  2.]  CHANGES  IN  NERVE  CELLS.  m 

Studied  the  changes  in  the  central  nervous  system  of  animals 
dying  from  varnishing  the  skin.  A  constant  symptom,  he  notes, 
is  hyperemia  of  spinal  cord  and  brain  with  numerous  capillary 
hemorrhages  in  the  gray  matter,  especially  of  cord  and  medulla. 
Extreme  vacuolation  is  the  most  characteristic  change  in  the 
Ipells. 

An  exhaustive  research  of  Sadovski  (73),  under  title,  "On 
the  changes  of  nerve  centres  due  to  peripheral  irritation,"  has 
for  its  purpose  "  to  ascertain  whether  pathological  changes  in 
the  centres  can  be  induced  by  irritation  of  a  nerve."  He  ac- 
cordingly stimulates,  or  better,  irritates  a  nerve,  generally  by 
ligature  ("from  10  to  71  days  "),  and  thereby  succeeds  in  causing 
neuritis  with  formation  of  a  "knot  about  the  size  of  a  pea" 
and  peripheral,  not  any  central,  degeneration  of  the  nerve. 
Microscopical  examination  of  the  ganglia,  using  those  of  the 
uninjured  side  for  controls,  showed  for  most  of  the  cells  no  dif- 
ference. Many  cells,  however,  on  the  operated  side  exhibited 
great  vacuolation  and  shrinking  of  protoplasm  from  the  capsule. 
The  nuclei  of  the  altered  cells  he  describes  as  "  oval  instead  of 
round,  densely  stained,  sometimes  shrunken  so  as  to  leave  a 
space  between  nucleus  and  protoplasm,  and  zigzag  in  outline." 
In  later  stages  no  trace  of  nucleus  is  present.  In  some  of  his 
experiments  Sadovski  employs  electrical  stimulation,  and  it  is 
difficult  to  understand  from  the  ground  of  my  own  experiments 
how,  in  Group  III,  experiment  5,  for  example,  a  moderate  stimu- 
lation of  only  fifteen  minutes  daily  for  twenty-one  days  could 
have  produced  the  vacuolated  protoplasm  and  shrunken  and 
atrophied  nuclei  that  he  describes  for  it  (73,  p.  30).  The  nerve, 
auricularis  magnus,  in  the  ear  of  a  dog  was  stimulated  through 
the  skin.  In  explanation,  Sadovski  advances  the  view  that  any 
such  additional  irritation  causes  the  nerve  cells  to  break  down 
more  rapidly  than  they  are  able  to  recover,  and  a  gradual 
"atrophy"  takes  place.  Hence  he  affirms  "it  is  possible  to 
demonstrate  morphological  changes  in  nerve  cells  due  to  exces- 
sive activity."     He  says  nothing  of  «crw^/ activity. 

Somewhat  similar  to  the  last  is  the  research  of  Mrs.  Ter- 
nowski  (80)  upon  "  Changes  in  the  spinal  cord  occasioned  by 
stretching  the  sciatic  nerve."  Among  other  things,  such  as 
hyperemia,  etc.,  vacuolation  and  atrophy  of  ganglion  cells 
is  noted  in  both  anterior  and  posterior  horns.     This  is  opposed 


112 


HODGE.  [Vol.  VII. 


to  Vulpian's  (82)  experiments  upon  guinea  pigs,  in  which  he 
was  unable  to  discover  any  changes  in  the  spinal  cord. 

Upon  the  purely  physiological  histology  of  nerve  tissue  little 
work  has  been  done. 

For  the  nerve  fibre,  Kiihne  notes  a  change  in  the  axis  cylinder, 
a  disarrangement  and  shrinking  together  of  the  fibrilae  with  the 
appearance  of  vacuoles  between  them,  in  the  nerves  of  the  nic- 
titating membrane  of  the  frog  due  to  only  ten  minutes'  unipolar 
stimulation  of  the  nerve  root  within  the  skull  (30,  p.  56 ;  Taf. 
D,  Fig.  64).  But  physiological  evidence  has  been  piled  up  by 
Bernstein  and  Widenskii,  and  later  by  Bowditch  (8  and  9) 
and  Szana  (79),  all  to  the  effect  that  a  nerve  fibre  is  not  sus- 
ceptible of  fatigue.  That  an  excised  nerve  dies  more  quickly 
when  stimulated  than  when  left  at  rest,  is  conclusively  proved 
by  Lee  (40) ;  and  why  this  should  occur,  if  no  change  associated 
with  activity  takes  place,  is  difficult  to  explain. 

For  the  nerve  cell,  possibly  the  observations  of  Svierczewski 
{78),  as  long  ago  as  1869,  have  a  physiological  bearing.  This 
observer  studied  the  cells  of  the  frog's  sympathetic  ganglia 
kept  alive  in  aqueous  humor  or  lymph,  and  subjecting  them  to 
different  conditions,  observed  the  effects.  From  what  more 
recent  work  is  bringing  to  light,  it  is  significant  to  note  that 
active  changes  were  discovered  only  within  the  nucleus.  The 
nucleoli  were  observed  to  wander  about  in  the  nucleus,  some- 
times in  a  most  lively  fashion,  for  as  long  as  twenty-four  hours. 
On  exposing  the  cells  to  carbon  dioxide,  a  finely  granular  pre- 
cipitate suddenly  formed  within  the  nucleus,  which  redissolved 
on  treatment  with  oxygen  or  hydrogen  ("paraglobulin-reaction"). 
This  process  was  accompanied,  under  certain  conditions,  by  a 
marked  shrinkage,  the  rounded  form  of  the  nucleus  being  altered 
to  an  irregular  or  "zickzack"  outline,  the  nucleolus  at  the  same 
time  being  lost  to  view. 

Somewhat  similar  observations  were  made  by  Freud  (13)  upon 
the  living  ganglion  cells  of  Astacus.  He  describes  shreds  and 
angular-shaped  particles  which  change  form  and  position  within 
the  nucleus. 

The  only  paper  devoted  to  the  exact  problem  in  hand  was 
written  in  1889  by  Bohdan  Korybut-Daszkiewicz  (32).  The 
author  states  the  exact  question  :  "  Is  the  activity  of  the  cen- 
tral nervous  system  accompanied  by  changes  recognizable  with 


No.  2.]  CHANGES  IJV  NERVE  CELLS. 

the  microscope?"     He  proceeds  to  answer  the  question  under 
the   idea    that    staining   reveals    much    finer   differences   than 
changes  of  form.     This  determines  his  method,  which  consists 
in  choosing  two  frogs  of  the  same  weight  and  sex,  the  one  to 
be  experimented  with,  the  other  to  use  as  control.     He  then 
stimulates  by  induction,  shocks  the  eighth  nerve  of  one  frog  for 
one  hour,  keeping  the  control  frog  as  quiet  as  possible  dirring 
the  same  time.     The  spinal   cords  of  both  are  now  removed 
and  hardened  in  corrosive  sublimate  solution  and  alcohol,  and 
sections   are   made  through   both,   opposite  the  origin  of  the 
eighth  nerve.     The  sections  are  stained  on  the  slide  with  he- 
matoxylin,  nigrosin,   eosin,   and  safranin   (the  Gaule  combina- 
tion), in  the  order  named.     In  some  cases,  the  author  states, 
sections  of  the  two  cords  were  treated  on  the  same  slide.     Here,' 
again,  interest  is  attracted  to  the  nuclei.     By  a  difference  in 
staining  these  fall  into  two  categories,  the  red  and  the  blue, 
and  a  greater  proportion  of  the  nuclei  stain  red  in  the  cord  of 
the  stimulated  frog.     A  count  of  all  red  and  all  blue  nuclei,  in 
a  large  number  of  sections,  shows  that  from  3.31  to  3.66  times 
more  nuclei  stain  red  in  the  stimulated  than  in  the  unstimu- 
lated frog.     The  results  are  derived  from  but  four  frogs,  two 
stimulated  and  two  control.^ 

Reproductive  tissues,  gland,  muscle,  and  nerve  have  thus 
been  worked,  with  a  purpose  of  demonstrating  microscopical 
changes  connected  with  functional  activity.  The  above  is  itself 
a  resume.  I  shall  not  attempt  a  resume  of  a  resume.  I  wish, 
however,  to  gather  in  a  few  words  the  ideas  having  special  bear- 
ing upon  my  own  work. 

1.  In  connection  with  reproduction,  the  nucleus  of  the  fertil- 
ized ovum  determines  the  form  of  the  whole  animal.  Each 
nucleus  determines  the  protoplasm  of  its  own  cell. 

2.  Protoplasm  may  be  of  the  nature  of  a  stable  mechanism, 

1  For  reasons  detailed  in  a  previous  paper  I  do  not  place  entire  confidence  in  the 
above  results  (24,  p.  384).  Such  a  difference  may  be  due  to  the  frogs  for  so  small 
a  nuniber  of  cases,  but  is  more  probably  due  to  a  difference  in  thickness  of  sections, 
as  I  have  found  that  thick  and  thin  sections  stain  differently  in  exactly  this  respect, 
the  nuclei  near  the  surface  of  the  section  staining  red,  those  deeper  down  staining 
blue.  Hence  the  thmner  the  section  the  greater  the  proportion  of  red-stained  nuclei, 
and  in  equal  areas  of  section  Daszkiewicz  finds  nearly  4CX)  (4127  to  3759)  less  nuclei 
in  the  stimulated  cord.  This  would  indicate  that  these  sections  are  thinner,  and  here 
he  finds  the  preponderance  of  red  nuclei. 


114 


HODGE.  [Vol.  VII. 


formed  by  the  nucleus,  under  normal  circumstances,  once  for 
all  (muscle,  connective  tissue,  etc.),  or  it  may  be  unstable  and 
be  formed  continuously  as  used  up  (gland).  In  the  former  case, 
nuclei  take  a  subordinate  place  in  the  tissue  after  the  mechanism 
is  built.  In  the  latter  case,  the  nuclei  retain  a  prominent  posi- 
tion throughout  the  life  of  the  tissue.  Granules  have  been 
observed  (Ogata)  streaming  out  of  the  nucleus  into  the  cell- 
protoplasm,  and  while  the  many  may  not  have  applied  methods 
suitable  for  demonstrating  this,  nothing  has  been  seen  which 
renders  the  fact  improbable.  For  an  instructive  discussion  of 
this  most  vital  of  all  points,  I  cannot  do  better  than  refer 
the  reader  to  De  Vries'  (lo,  pp.  180-187)  intracellulare  Pange- 
nesis. He  will  there  find  discussed  the  views  of  Haeckel  and 
the  Hertwigs,  Flemming  and  Strasburger,  Tangle,  Haberlandt, 
Korschelt,  Pringsheim,  Schmitz,  Nussbaum,  Gruber,  Hanstein, 
Weisman,  Klebs,  and  others,  all  of  whom  bring  here  a  point 
and  there  a  point  to  prove  that  out  of  the  nucleus  comes  every- 
thing of  structural  significance  in  the  protoplasm.  Read  also 
Altmann,  Elenientarorga7iismen  (2),  and  Die  Structnr  des  Zell- 
kems  (3). 

3.  In  no  cells  are  nuclei  more  prominent  than  in  ganglion 
cells.  Changes  have  been  observed  (Svierczewski  and  Freud) 
within  the  nuclei  of  nerve  cells,  and,  possibly,  differences  in 
staining.  Granulation  also  forms  a  characteristic  feature  of 
ganglion  cells.  This  resembles  in  appearance  the  unstable 
mechanism  of  gland  cells.  If  this  outward  resemblance  is  real, 
we  shall  find  changes  in  granulation  also. 

IV.    Effects  of  Electrical  Stimulation. 
Method. 

Throughout  this  series  of  experiments,  the  spinal  root  ganglia 
were  used.  The  scheme  of  procedure  was  to  stimulate  a  nerve 
going  to  one  or  more  of  these  ganglia  on  one  side  of  the  animal, 
leaving  the  corresponding  ganglia  of  the  other  side  at  rest,  to 
use  as  control.  To  avoid  confusion,  the  right  side  was  used  for 
stimulation,  the  left  for  control.  The  stimulated  nerve  was 
never  divided,  so  that  the  contraction  of  its  muscles  could  be 
used  to  indicate  the  healthy  condition  of  the  nerve.     If  a  nerve 


No.  2.]  CHANGES  IN  NERVE  CELLS.  115 

is  conducting  impulses  peripherally  to  its  muscles,  it  may  be 
taken  for  granted  that  it  is  conducting  impulses  in  like  manner 
centrally  to  its  ganglion. 

In  general,  as  a  means  of  stimulation,  the  ordinary  combina- 
tion was  used  of  Du  Bois  Reymond  coil,  platinum  electrodes,  and 
bichromate  or  copper  sulphate  cell ;  and  the  strength  of  stimulus 
was  determined  within  physiological  limits  by  touching  the  elec- 
trodes to  the  tongue  before  beginning  to  stimulate.  For  the 
first  few  experiments  the  animal  was  put  under  the  influence  of 
curare  and  the  stimulation  was  continuous.  Failing  of  any  re- 
sults, the  use  of  curare  was  abandoned  (39,  p.  523)  and  intervals 
of  rest  were  allowed.  At  first  this  was  managed  by  placing  a 
key  in  the  circuit  and  making  and  breaking  the  circuit  once  a 
minute  by  hand.  In  later  experiments,  this  was  relegated  to 
clockwork,  which  spaced  the  intervals  with  more  precision  and 
removed  the  chief  feature  of  irksomeness  from  the  operation. 

At  the  end  of  the  desired  length  of  time,  the  stimulated 
ganglion,  with  its  mate  of  the  opposite  side,  was  excised  as 
quickly  as  possible  and  the  process  of  fixing  and  hardening 
begun.  The  method  from  this  point  on  is  directed  toward 
having  the  two  ganglia  pass  through  identical  treatvtent.  In  no 
instance  were  they  separated  from  the  time  they  left  the  animal  to 
the  time  when,  placed  side  by  side  7ipon  the  same  slide,  they  appeared 
tinder  the  microscope  for  study.  Not  only  were  they  carried  through 
the  same  reagents,  but,  in  every  case  through  the  same  reagents 
iti  the  same  bottles  or  disJies  from  tJie  first  fixing  fluid  to  the  solid 
para  fin.  And  further,  the  two  are  cut  at  the  same  stroke  of  the 
microtome  knife,  fixed  to  the  slide  together,  stained  together,  and 
appear  side  by  side  in  the  same  field  of  the  microscope. 

The  carrying  of  a  large  number  of  specimens  through  the 
hardening  and  embedding  and  cutting  processes,  keeping  each 
distinct,  was  greatly  facilitated  by  the  following  simple  device. 
At  first  slips  of  mica  were  used,  but  a  thin  hard  cardboard  was 
found  to  be  more  convenient.  This  is  cut  into  strips,  —  3  x  i  cm. 
is  a  good  size,  —  and  the  ganglia,  which  are  carried  up  to  strong 
alcohol  attached  to  their  segment  of  the  cord,  are  trimmed  for 
cutting  and  arranged,  the  two  to  be  compared  touching  each 
other,  upon  one  end  of  the  strip  of  cardboard.  A  drop  of  the 
white  of  an  egg  is  now  placed  over  them,  allowed  to  dry  some- 
what, and  the  whole  carefully  laid  in  alcohol.     The  albumen  is 


jjg  HODGE.  [Vol.  VII. 

speedily  coagulated  and  holds  the  ganglia  firmly  to  each  other 
and  to  the  slip.  The  rule  of  always  placing  the  stimulated 
ganglion  nearest  the  end  of  the  slip  aids  in  simpHfying  matters. 
Any  desired  record  may  be  written  upon  the  other  end  of  the 
slip  and  all  the  trouble  of  keeping  a  number  of  little  indistin- 
guishable things  from  becoming  mixed  up  is  at  once  done  away 
with.  The  cards  are,  of  course,  embedded  with  the  ganglia 
attached.  They  can  easily  be  removed,  if  desired,  for  cutting  ; 
but  I  generally  place  the  specimens  so  that  the  plane  of 
cutting  shall  be  parallel  to  the  card.  In  cutting,  it  has  been 
my  practice  to  give  the  face  of  the  paraffin  block  the  shape 
of  a  trapezoid,  with  the  stimulated  ganglion  always  toward  the 
shorter  side.  Each  section  then  carries  a  record  of  the  arrange- 
ment of  specimens  within  it,  and  any  number  of  sections  may 
be  cut  and  stored,  with  no  danger  of  confusion.  Not  only  one, 
but  several  pairs  can  be  fastened  to  the  same  slips  arranged 
in  a  row  so  that  they  may  all  be  cut  at  the  same  time.  For 
example,  it  was  my  practice  to  stimulate  the  right  brachial  and 
sciatic  plexuses  of  a  frog :  this  places  at  our  disposal  five  pairs 
of  ganglia ;  each  pair  may  be  hardened  in  a  different  way,  and 
all  be  arranged  as  described  above  on  a  single  slip.  They  are 
all  cut  together,  fixed  to  the  slide  (by  alcohol  fixative  method), 
and  all  stained  together.  Many  slides  are  obtainable  from  one 
such  set  of  ganglia,  and  each  slide  may  be  stained  in  a  different 
way.  Thus,  incidentally,  a  permutation  of  hardening  and  stain- 
ing combinations  has  been  obtained  which  might  form  the 
basis  of  a  separate  study. 

Not  only,  in  this  way,  may  a  dozen  specimens  be  manipulated 
as  easily  as  one,  but  they  are  held  in  the  desired  positions  rela- 
tive to  each  other,  and,  of  special  importance,  they  are  cut 
together.  However  perfect  the  microtome,  sections  do  not 
always  come  from  it  of  absolutely  uniform  thickness ;  and  where 
minute,  or  even  gross,  differences  of  granulation  or  staining  are 
to  be  studied,  this  is  of  prime  importance. 

The  essential  feature,  then,  of  my  method  is  that  it  compares 
corresponding  ganglia  of  the  same  animal -which,  have  been  sub- 
jected to  identical  treatment  in  passing  from  the  animal  to  the 
slide,  the  only  point  of  difference  being  that  one  has  had  its  nerve 
stimulated  for  a  longer  or  shorter  time,  while  the  other  has  not. 
Methods  of  hardening  and  staining  do  not  concern  us  so  long  as 


No.  2.]  CHANGES  IN  NERVE  CELLS.  117 

the  two  ganglia  to  be  compared  go  through  every  step  of  the 
process  together. 

Almost  every  method  has  been  tried  in  the  hope  of  obtaining 
some  striking  reaction.  Some  such  were  found,  but  up  to  date 
they  have  all  proved  inconstant.  Trzebinski  (81)  has  made  a 
special  study  of  the  influence  of  hardening  reagents  upon  the 
ganglion  cells  of  the  spinal  cord.  He  finds  corrosive  sublimate 
one  of  the  best  reagents,  and  states  that  it  does  not  produce 
vacuolation  of  the  cell.  This  method,  followed  by  Gaule's  quad- 
ruple staining,  has  given  the  best  preparations  for  the  study  of 
granulation  and  staining  (see  PI.  I,  Figs.  3-5).  Trzebinski,  it 
would  seem,  did  not  experiment  with  osmic  acid.  This,  with 
hsematoxylin  and  safranin,  or  all  four  of  the  Gaule  stains,  has 
given  a  most  perfect  preservation  of  the  form  of  the  nucleus  and 
the  minute  structure  of  the  cell  protoplasm.  Altmann's  methods 
(2)  have  been  tried  a  number  of  times,  but  although  beautiful 
preparations  of  gland  tissues  were  obtained,  nothing  definite  was 
brought  out  in  nerve  cells. 

Two  widely  different  animals,  the  frog  and  cat,  were  purposely 
selected,  upon  which  to  experiment.  The  results  which  I  will 
now  pass  to  consider  are  derived  from  fifteen  experiments  upon 
frogs  and  eleven  upon  cats.  All  the  experiments  will  be  referred 
to  either  singly  or  in  groups. 

Results. 

For  sake  of  brevity  little  more  than  a  tabulation  of  the  results 
will  be  given.     For  further  details,  see  a  former  paper  (24). 

Frog  No.  I  was  given  three  drops  of  one  per  cent  curare  solu- 
tion and  right  sciatic  nerve  was  stimulated  continuously  for 
thirty  minutes.  The  three  pairs  of  sciatic  ganglia  were  excised 
and  with  those  of  a  control  frog  hardened  in  corrosive  sublimate. 
The  ninth  pair  were  stained  in  toto  in  soda  carmine,  and  for  some 
unaccountable  reason  scarcely  any  nucleoli  could  be  found  in 
sections  of  the  stimulated  ganglion,  while  they  appeared  as  usual 
in  the  ganglion  of  the  other  side  and  in  the  control  ganglia.  A 
count  of  the  two  gave  the  following  :  — 

nuclei         nucleoli 

,  (  resting,  122         92 

Six  sections  of  each  contamed  j  stin^ui^ted,         177         28 


Ilg  HODGE.  [Vol.  VIL 

Expressed  in  per  cent,  75  +  %  of  the  nuclei  in  the  resting  gan- 
glion contained  nucleoli  to  1 5  +  %  in  the  stimulated.  The  sev- 
enth and  eighth  pairs,  stained  in  other  ways  (Kleinenberg's 
h£ematoxylin  and  by  Weigert's  method),  gave  no  such  result. 
In  fact,  the  phenomenon  could  not  be  made  to  reappear  in  any 
subsequent  experiment. 

Next,  three  similar  frogs  were  taken,  each  with  a  control ; 
each  was  given  the  same  amount  of  curare  and  the  right  sciatic 
nerves  of  the  three  were  stimulated  continuously  one,  two,  and 
three  hours  respectively.  From  the  nine  stimulated  ganglia  no 
effect  of  activity  could  be  made  out. 

Frogs  5  and  6  were  used  respectively  to  test  the  effect  of 
curare  and  the  extent  of  post-mortem  changes  in  ganglion  cells, 
with  results  that  do  not  concern  us  here  farther  than  to  say  that 
the  use  of  curare  was  abandoned  ^  and  the  ganglia  were  excised 
as  quickly  as  possible  after  death.  At  this  point  it  was  also 
decided  to  use  intermittent  instead  of  continuous  stimulation. 

Frog  No.  7  was  made  reflex,  and  the  right  brachial  and  sciatic 
plexuses  were  stimulated,  with  two  minutes'  stimulation  alter- 
nating with  two  minutes'  rest,  for  two  and  a  half  hours.  Marked 
differences  between  the  cells  of  the  two  sides  are  clearly  visible. 
Perhaps  the  most  pronounced  of  these,  a  difference  noted  inde- 
pendently by  a  number  of  observers,  is  that  the  nuclei  appear 
shrunken  in  the  stimulated  ganglia.  This  led  to  the  series  of 
measurements  summarized  in  the  following  table.  The  nuclei 
were  measured,  long  and  short  diameters  in  sets  of  one  hundred, 
fifty  stimulated  and  fifty  unstimulated  being  taken  from  as 
nearly  corresponding  sections  of  the  two  ganglia  as  possible.  A 
definite  rule  precluded  wilful  selection  of  the  cells  to  be  meas- 
ured, this  rule  being  that  only  nuclei  containing  nucleoli  should 
be  measured,  and  that  all  such  should  be  taken  in  the  order  of 
their  occurrence  in  the  section.  Measurements  were  made  with 
an  eye-piece  micrometer  to  the  nearest  /i  under  magnification  of 
Leitz  oc.  3,  obj.  7  (=  600  diameters). 

1  Landois  and  Sterling,  Physiology,  p.  523,  reads:  "But  when  the  action  of  the 
drug  (curare)  is  fully  developed,  no  amount  of  stimulation  of  the  skin  or  the  posterior 
roots  of  the  nerves  vi^ill  give  rise  to  a  reflex  act,  although  the  motor  nerve  of  the  liga- 
tured limb  is  known  to  be  excitable."  My  experiment  on  frog  5,  in  which  all  but  the 
sciatic  nerve,  bone  a7id  all,  was  severed,  gave  exactly  the  above  result.  The  reason 
for  absence  of  results,  however,  in  my  case,  may  have  been  continuous  stimulation  or 
curare  or  both. 


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No.  2.]  CHANGES  IN  NERVE  CELLS. 

y 

TABLE   I. 

Frog  No.  7,  made  reflex.  Stimulated  two  and  one-half  hours, 
intervals  of  rest  and  stimulation  being  two  minutes.  Three 
sets  of  one  hundred  nuclei  each. 

Nuclei  in  M  Cells  in  ^ 

mean  diameters.  mean  diameters. 

f.b    c  Resting 13.57. 

Stimulated 12.23  \  Set  i. 

.5  ^        50*-  Diff. 1.34  J 

Resting 13.94  ■) 

Stimulated 1 2.56  [•   Set  2. 

Diff. ^TT^si 

Resting 14.48  \ 

Stimulated 13.26  \   Set  3. 

Diff. "1.22  J 

Sets  I,  2,  and  3,  volume  shrinkage,  24  %.l 

The  five  succeeding  experiments  were  made  with  the  purpose 
of  getting  the  greatest  possible  amount  of  change ;  and  under 
the  supposition  that  this  might  be  obtained,  for  the  frog  at 
least,  in  shorter  time,  if  the  nutrition  of  the  cells  was  prevented, 
the  frogs  were  thoroughly  bled  or  the  capsules  of  the  ganglia 
torn  off.  None  of  these  experiments  gave  definite  results. 
Sections  of  both  ganglia  appear,  stained  by  Gaule's  method, 
redder  than  normal,  indicating  apparently  a  clogging  of  the 
cells  with  decomposition  products.  Stimulated  and  resting 
show  alike  vacuolation,  perhaps  the  same  as  that  observed 
by  Rosenbach  {6?,)  in  starving  dogs.  The  nuclei  in  both  are 
shrunken,  but  show  no  marked  difference  in  size. 

Results  of  a  single  experiment  of  this  class  need  be  given. 

TABLE   n. 

Frog  No.  8,  bled.  Stimulated  for  seven  hours,  five  minutes 
of  stimulation  alternating  with  five  minutes  rest.  One  set  of 
one  hundred  nuclei. 

Mean  diameters 
in  /u. 
Oanglia  of  8th   pair,    hardened  in  -j 

corrosive  subhmate  and  stained   I  ^^^ting 12.36  I    Volume  shrinkage, 

by  the  Gaule  method.  i   Stimulated i2.oi   i  8  %. 

'  The  volume  shrinkage  per  cent  is  computed  from  the  mean  diameters,  treating 
the  nuclei  as  spheres. 


I20 


HODGE. 


[Vol.  VII. 


One  experiment,  in  which  the  ganglia  were  suspended  in  a 
large  beaker  of  sterilized  normal  salt  solution,  gave  more  definite 
results. 

TABLE   III. 

Frog  No.  14.  Sciatic  ganglia  of  right  side  suspended  in  salt 
solution  and  stimulated  three  and  one-half  hours,  five  stimuU 
per  second,  one  minute  of  stimulation  alternating  with  one 
minute  of  rest.  The  ganglia  of  left  side  kept  during  this  time 
in  blood  of  same  frog.     Two  sets  of  one  hundred  nuclei  each. 


Mean  diameters 
in  /u.. 


Resting 

Stimulated. 
Diff. . . . 


14.70 

13-10 
1.60 


I 


Resting 14.57 

Stimulated. .    12.14 
Diff.....     2.43 


Set  I.  —  Measured  by  myself  previous  to  Mr. 
W.'s  measurement  of  set  2. 

Set  2. 


J 


Measured  by  Mr.  W.  without  knowl- 
edge of  my  results,  and  having  but  one  of 
the  ganglia  in  the  field  at  the  same  time, 
and  not  knowing  which  had  been  stimulated 
and  which  not. 
Sets  I  and  2,  volume  shrinkage,  36  %. 

Thinking  that  greater  changes  might  be  obtained  at  a  higher 
temperature,  one  experiment  was  made  to  test  this ;  and,  though 
not  entirely  successful,  the  result  may  be  given. 


TABLE  IV. 

Frog  No.  15.  Cerebrum  removed,  and  wound  allowed  to 
heal  before  experiment.  Stimulated  five  and  one-half  hours  at 
temperature  35°  C. ;  intervals  of  rest  and  stimulation,  one 
minute.     Two  sets  of  one  hundred  nuclei  each. 


bo  - 


W 


Mean  diameters 
in  |U,. 

Resting 16.53  1 

Stimulated....   15.66  \ 

Diff ~:87  i 

Resting 1740  ] 

Stimulated....    15.84  I 

Diff "1:56  I 


••s  r 

^  G  -    I   Restmg 20.90 

-!   Stimulated.... 


Diff. 


1913 
1.77 


Set  I.  —  Measured  by  xa^%€il  previous  to 
measurement  of  set  2. 

Set  2.  —  Measured  by  Mr.  L,  without 
knowledge  of  my  own  measurements, 
and  not  knowing  which  of  the  ganglia 
had  been  stimulated. 


Set  3. 


Sets  I,  2,  and  3,  volume  shrinkage,  12.5  %. 


No.  2.]  CHANGES  IN  NERVE   CELLS.  \2\ 

It  may  be  noted  that  both  Mr,  W.'s  and  Mr.  L.'s  measure- 
ments make  the  difference  greater  than  my  own.  Staining  and 
structure  of  protoplasm  not  well  defined  ;  due  probably  to  the 
fact  that  the  frog  died  toward  end  of  experiment.  At  its  close 
the  muscles  were  beginning  to  pass  into  rigor  mortis. 

It  was  thought  desirable  at  this  stage  to  ascertain  whether 
the  results  above  detailed  for  frogs  hold  good  for  a  mammal. 
So  far,  experiments  have  shown  that  the  most  marked  results 
are  to  be  obtained  by  keeping  the  animal  in  the  most  normal 
condition.  Functional  activity  of  the  nerve  cells  of  a  mammal 
can  certainly  not  be  studied  many  seconds  after  the  circulation 
is  stopped ;  whereas  an  animal  is  active  for  hours  at  a  time,  and 
the  experiments,  if  success  is  to  be  attained,  must  be  continued 
for  a  similar  time.  I  think  I  am  justified  in  distrusting  the 
influence  of  curare  even  upon  the  central  portion  of  the  reflex 
arc.  Narcotics  and  anaesthetics,  although  they  do  not  stop  the 
cardiac  and  respiratory  movements,  if  given  in  proper  amount, 
produce  most  profound  changes  in  the  activity  of  nerve  centres. 
So  far  as  known,  they  may  or  they  may  not  cause  correspond- 
ingly marked  histological  changes  in  the  nerve  cells.  However 
this  may  be,  it  was  determined  to  run  no  risk  of  complicating 
matters  by  their  use,  and  accordingly  a  method  of  producing 
insensibility  without  the  use  of  drugs  was  resorted  to. 

The  cat  was  chosen  for  farther  experiment.  The  method  ^  of 
procedure  is  briefly  as  follows :  The  cat  is  laid  on  a  holder  and 
gently  brought  under  the  influence  of  ether.  When  fully  anaes- 
thetized, the  skull  is  trephined  at  about  the  parietal  eminence, 
and  a  slit  made  through  the  dura,  care  being  taken  to  dodge 
any  blood-vessels  which  may  be  in  the  neighborhood.  The 
trephine  used  was  about  5  mm.  in  diameter.  With  kittens  it  is 
possible  to  lift  out  a  small  piece  of  bone  with  the  point  of  a 
knife-blade  with  generally  less  loss  of  blood  than  is  occasioned 
by  trephining.  Now,  holding  the  head  with  the  left  hand,  the 
thumb  upon  the  vertex,  the  tip  of  the  first  finger  upon  the 
angle  of  the  right  jaw,  the  tip  of  the  third  finger  upon  that  of 
the  left  jaw,  introduce,  through  the  opening  in  the  skull,  the 
blunt  end  of  a  3  mm.  glass  rod,  and  aim  it  directly  at  the  angle 

^  This  method  was  obtained  from  a  paper  entitled  "  On  the  renal  circulation  dur- 
ing fever"  (Walter  Mendelson,  Amer.  Jour.  Med.  Set.,  Phila.,  1883),  where  the 
method  is  credited  to  Ludwig. 


122 


HODGE.  [Vol.  VII. 


of  the  right  lower  jaw,  the  opening  being  invariably  made  in 
the  left  parietal  bone.  The  probe  will  strike  the  floor  of  the 
skull,  having  pierced  the  right  optic  thalamus  and  the  right 
crus.  Work  the  probe  across  the  floor  of  the  skull  about  3  mm, 
to  either  side  of  its  first  position  and  withdraw  it.  Introducing 
the  probe  again,  direct  it  forward  as  before,  but  directly  ventral, 
aiming  to  pierce  the  left  optic  thalamus  and  left  crus.  Take 
about  one  3  mm.  step  with  the  end  of  the  probe  to  right  and 
left,  withdraw  probe,  and  close  the  skin  over  the  wound.  The 
purpose  of  the  operation  is,  of  course,  to  destroy  sensibility  in 
the  cerebrum  and  to  cut  off  the  sensory  and  motor  tracts  in  the 
crura ;  and  if  successful,  complete  anaesthesia,  with  normal 
pulse  and  respiration,  should  result.  Remove  the  ether  imme- 
diately and  allow  the  animal  to  recover.  It  should  show  no 
signs  of  pain  or  distress,  but  should  remain  as  though  sleeping 
quietly  during  the  rest  of  the  experiment.  In  some  cases,  how- 
ever, the  animal  does  become  restless  for  a  few  minutes  after 
the  ether  passes  off.  This  condition  generally  lasts  but  a  short 
time  and  gives  place  to  the  state  of  quiet  sleep  desired.  After 
this  treatment  stimulation  may  go  on  for  any  reasonable  length 
of  time  with  no  further  trouble.  I  can  recommend  the  method 
to  any  who  wish  to  make  prolonged  experiments  not  involving 
the  returning  of  the  animal  to  consciousness.  It  is  not,  of 
course,  always  successful.  In  some  cases,  the  respiratory  centre 
becomes  involved,  spasmodic  gasping  sets  in,  and  unless  arti- 
ficial respiration  be  employed,  the  experiment  is  at  an  end. 
Examination  has  shown  that  this  is  due  generally  to  hemorrhage 
spreading  downward  from  the  section  in  the  crura  into  the  sub- 
stance of  the  medulla  or  between  the  medulla  and  floor  of  the 
skull.  Consequently  the  probe  should  be  so  manipulated  as  to 
injure  the  blood-vessels  in  the  floor  of  the  skull  as  little  as 
possible. 

The  next  step  is  to  get  the  electrodes  over  the  desired  nerves  ; 
and,  throughout  the  experiments,  the  nerves  of  the  right  bra- 
chial plexus  were  employed.  Turning  the  animal  upon  its  back, 
expose  the  external  pectoral  muscles  by  an  incision  through 
the  skin  about  two  inches  long  midway  between  the  sternum 
and  axilla.  Cutting  now  through  the  pectoral  muscles  will  ex- 
pose the  subclavian  artery  and  vein,  and  just  underneath  these 
can  be  seen  the  nerves  of  the  brachial  plexus.     In  order  to  pre- 


No.  2.]  CHANGES  IN  NERVE  CELLS.  123 

vent  hemorrhage,  I  always  take  the  muscles  up  with  a  double 
row  of  ligatures  and  make  the  cut  between  them.  Carefully- 
free  the  plexus  from  fat  for  a  short  distance  and,  without  injury 
to  the  nerves  or  blood-vessels  going  to  them,  separate  them  from 
the  subclavian  vessels,  and,  not  including  these,  slip  over  the 
plexus  from  behind  a  two-tined  platinum  electrode.^  Thus  the 
current  is  made  to  pass  through  the  nerves  obliquely.  By  in- 
cluding the  whole  plexus  at  this  point,  four  ganglia  are  stimu- 
lated. As  in  the  frog  experiments,  the  nerves  are  not  divided, 
and  as  the  stimulation  begins,  every  muscle  of  the  right  leg 
should  contract.  This  is,  in  fact,  the  test  of  the  proper  work- 
ing of  the  experiment. 

The  animal  is  now  to  be  carefully  tended  while  the  stimulation 
proceeds.  The  temperature  is  frequently  taken  and  heat  applied 
or  withdrawn  as  the  case  demands.  Respiration  and  pulse  are 
watched.  Lymph  is  apt  to  collect  in  the  axilla  about  the  elec- 
trodes and  should  be  frequently  wiped  up  with  absorbent  cotton. 
With  the  electrodes  in  place,  the  skin  is  drawn  together  over 
the  wound  and  held  with  a  clamp,  and  the  wound  is  further 
protected  by  an  ample  pad  of  cotton.  In  my  experiments, 
strictly  antiseptic  precautions  were  not  taken.  All  tools,  how- 
ever, which  touched  either  the  wound  in  the  head  or  axilla  were 
sterilized  before  each  operation ;  and,  in  no  case,  did  any  per- 
ceptible inflammation  make  its  appearance.  As  before,  the  mate 
ganglia  of  the  left  side  were  in  all  cases  used  as  control.  A 
double  control  was  employed  at  first,  consisting  of  a  pair  of 
thoracic  ganglia  from  the  same  animal  carried  through  with 
each  pair  of  test  ganglia.  This  was  soon  found  to  be  unneces- 
sary, since  the  cells  of  these  control  ganglia  resembled  those  of 
the  resting  ganglion.  The  results  of  the  first  experiment  may 
be  read  from  the  following  table :  — 

'  The  electrode  first  used  was  the  platinum-tipped  electrode  ordinarily  used  to 
stimulate  muscle-nerve  preparations.  Thinking  that  it  would  be  better  to  have  the 
platinum  tips  guarded,  I  made  an  electrode  by  letting  heavy  copper  wires  into  deep 
saw  grooves  in  a  strip  of  gutta-percha.  The  platinum  wires  were  soldered  to  these 
and  were  made  to  lie  half- exposed  in  shallow  grooves  upon  the  inner  side  of  each 
of  two  fork-like  prolongations  of  the  gutta-percha. 


124 


HODGE. 


[Vol.  VII. 


TABLE   V. 

Cat  No.  I.     Stimulated  for  seven  hours  ;  intervals  one  minute, 
spaced  by  hand. 


Nuclei  (4  sets, 

100  each) . 

Cells. 

Mean  diameters 

Shrinkage        y\ 

ean  diameters 

in  n. 

in  volume. 

in  \i.. 

ist  thoracic.     Hardened  /  Resting 

in  osmic  acid.                  *•  Stimulated. 

16.29 

59.06 

14.07 

35% 

57-19 

Diff.... 

.       2.22 

8th  cervical.     Hardened  /  Resting 

;        in  corrosive  sublimate.   I  Stimulated. 

14.91 

(Selected.) 

All  over 

11.70 

51  %  (T.) 

50  i"- 

^                                                           Diff.... 

.       3-21 

3    7th  cervical.     Hardened  /  Resting 

^        in  riemming's  fluid.        I  Stimulated. 

.     16.60 

57-5° 

•     I54I 

20% 

56.25 

Diff. . . . 

.       1. 19 

6th  cervical.     Hardened  /  Resting 

in  picric  acid.                  I  Stimulated. 

14.98 

44.21 

•     14-23 

14.6  % 

44-74 

Diff. . . . 

•       -75 

Sets  I,  2,  3,  4,  volume  shrinkage, 

28.6  %. 

Several  points  in  the  above  table  call  for  remark.  The  seat 
of  most  active  change  is  again  seen  to  be  within  the  nucleus. 
It  is  to  be  noted  also  that  the  greatest  amount  of  difference 
between  resting  and  stimulated  nuclei  occurs  in  the  ist  thoracic 
and  8th  cervical  ganglia.  This  may  be  due  to  the  fact  that  a 
greater  number  of  the  nerves  from  the  6th  and  7th  cervical 
ganglia  escape  stimulation.  Or  it  may  be  that,  coming  first 
between  the  electrodes,  the  branches  from  the  ist  thoracic  and 
8th  cervical  tend  to  short  circuit  the  current  and  thus  deprive 
the  others  of  a  due  share  of  the  stimulation.  At  any  rate,  the 
6th  and  7th  cervical  have  failed  to  show  the  effect  of  stimula- 
tion to  the  extent  shown  by  the  8th  cervical  and  ist  thoracic; 
and  for  clearest  results  I  have  found  it  best  to  include  in  the 
circuit  the  medius  and  spiralis  nerves,  with  the  small  branches 
lying  between  and  behind  these,  and  then  use  only  the  8th 
cervical  and  ist  thoracic  ganglia.  Another  word  of  explanation 
may  be  added.  It  must  be  taken  into  account  that,  in  clasping 
the  whole  plexus  between  the  tines  of  the  electrode,  we  are 
stimulating  an  enormous  number  of  nerves.  When  the  strength 
of  the  stimulation  is  tested,  if  the  tip  of  the  electrode  only  is 
touched  to  the  tongue,  the  stimulation  is  concentrated  on  a 
small  area  and  affects  but  a  few  nerve  fibres.     The  stimulation 


No.  2.]  CHANGES  IN  NERVE  CELLS.  125 

is  hence  felt  to  be  severe ;  whereas  if  the  electrodes  are  laid 
full  length  upon  the  tongue,  the  stimulus  can  scarcely  be  felt 
at  all.  The  neglect  of  this  fact  at  first  has  resulted  in  the  use 
of  quite  inadequate  stimulation. 

Stimulation  in  this  case  was,  however,  severe.  It  was  fre- 
quently increased  by  sliding  up  the  secondary  coil,  and  was  so 
regulated  as  to  produce  the  greatest  possible  amount  of  muscu- 
lar contraction  in  the  right  fore  leg  without  causing  reflex  con- 
tractions in  other  parts  of  the  body.  Contractions  in  this  leg 
toward  close  of  experiment  were  feeble  but  constant.  Within 
five  minutes  after  the  animal  was  bled,  the  muscles  of  this  leg 
had  passed  into  rigor  fnortis,  the  muscles  of  all  the  other  limbs 
being  normal  and  irritable.  Pulse  and  respiration  remained 
normal  the  whole  time. 

Aside  from  shrinkage  of  the  nuclei,  other  important  changes 
occur.  For  the  ist  thoracic  pair,  hardened  in  osmic  acid,  the 
nuclei  are  plump  and  round  in  the  resting  ganglion,  and  stain 
lighter  than  the  cell  protoplasm.  In  the  stimulated  ganglion 
they  are  irregular  in  outline  and  stain  much  darker  than  the 
rest  of  the  cell.  This  appearance  is  due  not  only  to  a  darker 
staining  of  the  nucleus,  but  to  a  lighter  staining  of  the  cell. 
Holding  the  osmic  acid  sections  of  resting  and  stimulated  gan- 
glia over  a  white  surface,  it  is  not  difficult  to  see  with  the 
unaided  eye  that  the  resting  ganglion  is  stained  darker  than  the 
other.  This  indicates  that  a  substance  which  reduces  osmic 
acid  has  been  used  up  or  changed,  in  the  stimulated  cell,  into 
something  which  does  not  reduce  the  acid  ;  while  in  the  nucleus 
more  of  something  which  reduces  osmic  acid  has  been  produced 
during  stimulation.  Examined  microscopically,  the  lighter  stain 
is  seen  to  be  due  to  extreme  vacuolation  of  the  cell  protoplasm. 
This  does  not  occur  in  the  resting  ganglion  of  the  left  side  or 
in  the  two  thoracic  ganglia  used  as  control.  The  general  appear- 
ance is  well  shown  in  Figs,  i  and  2  of  PI.  VII ;  although  the 
vacuolation  of  the  cell  protoplasm  in  Fig.  2  has  not  been  well 
copied  from  the  original  drawing.  The  protoplasm  of  all  the 
cells  shows  definite  vacuolation  to  a  greater  or  less  extent.^  It 
was  also   noticed  indepetidently  by  three  ^  observers   that  the 

^  This  appearance  is  better  represented  in  Figs.  3  and  4,  Amer.  Jour.  Psy.,  Vol. 
II,  p.  403. 

*  The  three  were  Dr.  II.  II.  Donaldson,  Dr.  Wm.  II.  Welch,  and  the  author. 


126  HODGE.  [Vol.  VII. 

nuclei  of  the  cell  capsule  were  shrunken  in  the  stimulated  gan- 
glion. This  may  be  seen  by  comparison  of  Figs.  2,  4,  and  5 
with  Figs.  I  and  3  of  PI.  VII,  and  holds  good  also  for  diurnal 
fatigue,  for  which  compare  the  capsular  nuclei  of  Figs.  7  and  6, 
PI.  VIII.  This  may  indicate  the  supposed  nutritive  function  of 
the  capsular  cells. 

The  8th  cervical  ganglia,  hardened  in  corrosive  sublimate, 
show  for  the  right  ganglion  the  shrunken  and  darkly  stained 
nuclei  characteristic  of  stimulation  (compare  nuclei  in  Figs.  3 
and  4,  PI.  VII).  The  vacuolation  of  the  protoplasm  is  not  brought 
out,  although  well  preserved  by  the  same  method  in  some  of 
the  frog's  ganglia.  Flemming's  fluid  and  picric  acid  happened 
to  be  used  here  by  way  of  experiment,  but  were  found  to  give, 
on  the  whole,  inferior  results. 

TABLE  VI. 

Cat  No.  2.  Stimulated  one  hour  forty  minutes;  intervals 
one  minutes. 

100  Nuclei.  iqo  Cells. 

Mean  diameters  Shrinkage               Mean  diameters 

in  y-  in  volume.                         in  /u.. 

Ganglia  ist  thoracic,    f  Resting 14.91  48.10 

Osmic  acid.           I  Stimulated 13.51  25.6%                    46.53 

Diff. "740 

Examination  of  sections  shows  similar  changes  to  those 
described  for  cat  No.  i,  but  much  less  in  degree. 

No  attempt  was  made  to  render  the  stimulation  equal  in  the 
two  experiments ;  but  it  is  strongly  hinted  by  the  results  that 
a  quantitative  relation  exists  between  the  amount  of  stimula- 
tion and  amount  of  change  in  the  cells.  Such  a  relation  should 
obtain,  if  we  are  dealing  with  physiological  cause  and  effect.  To 
test  the  point  with  mathematical  precision  is,  of  course,  impossi- 
ble ;  for  we  must  know,  in  order  to  do  this,  not  only  the  strength 
of  stimulus  used,  but  also  that  the  same  amount  of  stimulus  is 
distributed  to  the  same  number  of  cells ;  and,  further,  that  the 
ganglion  cells  of  one  animal  are  exactly  as  irritable  as  those  of 
another  animal.  However,  to  decide  the  matter,  a  series  of 
experiments  was  arranged  under  the  assumption  that  the  irrita- 
bility of  cats  is  in  general  the  same,  and  that  the  same  nerves 
m  different  cats  connect  approximately  with  the  same  number 
of  ganglion  cells.     To  make  these  factors  as  nearly  alike  as  pos- 


No.  2.] 


CHANGES  IN  NERVE  CELLS. 


127 


sible,  half-grown  kittens  were  used  throughout.  The  strength 
of  stimuli  was  regulated  by  placing  a  rheocord,  resistance-box, 
and  galvanometer  in  the  primary  circuit  derived  from  two  i  1. 
copper  sulphate  cells.  By  manipulation  of  the  resistance-box 
and  rheocord,  the  galvanometer  needle  was  brought  to  a  given 
position  and  held  at  this  point  during  the  whole  of  each  experi- 
ment. The  experiments  were  made  in  rapid  succession  and 
without  altering  the  setting  of  the  apparatus.  Stimuli  were 
purposely  not  severe,  because  of  the  long  duration  of  some  of 
the  experiments.  But  not  until  the  series  had  been  studied 
was  it  clear  that  the  stimulation  was  too  slight  for  the  most 
definite  results. 


5    o      • 

cm"" 
o    c  .0 

3         o 
S  ^    c 

•X3     <«    "^ 


TABLE 

VII. 

Series  with  Equal  Stimulation. 

Length  of 
stimulation. 
'  Cat  No.  7    (operated 
upon  and  left  without 
stimulation  2\  hrs.) .     0  hrs. 

No.  of 

nuclei         Mean  diameters 
measured.               in  p., 

100                   14.20 

Shrinkage 
in  volume 
of  nucleus. 

^-    6.9% 

1454 

Cat  No.    5 i   " 

100 

14.70 
13-51 

+  22  0/, 

Cat  No.    6 z\" 

200(T.)« 

11.86 

10.9s 

+  21% 

Cat  No.    8 5  " 

100 

15-97 
14.38 

+  24.3% 

Cat  No.  i  i 10  " 

100 

8S.  100 

S.  100  (T.) 
100  (T.) 

16.19 
13-35 

+  43-9% 

■"  "in  C 

"c  "^  ij 

O  ~  w 

u  °  c« 

qj  o  f* 

S  0)  -^ 

i/i  .. 

"  ^"^ 

^^  ^  Ol, 

jn  .—  'Jj 

C  M  O 


Two  experiments  were  made  to  test  the  effect  of  stronger 
stimulation  and  the  influence  of  the  rest  interval,  with  the 
suggestive  result  expressed  by  Table  VIII. 

1  The  minus  sign  indicates  that  the  nuclei  of  the  right  side  are  slightly  larger  in 
this  case.  In  the  only  other  set  measured  from  a  normal  pair,  the  nuclei  were  also 
a  little  larger  on  the  right  side. 

2  Sets  marked  "  T."  are  measured  by  a  third  person,  with  whom  every  precaution 
was  taken  to  obtain  purely  mechanical  and  unprejudiced  measurements. 

'  Sets  marked  "  S."  (selected)  are  those  in  which  only  nuclei  in  cells  of  over  50  /* 
diameter  were  measured.  The  shrinkage  volume  per  cent  is  given  for  the  two 
unsclectcd  sets,  not  marked  "  S,"  and  are  thus  comparable  with  other  members  of 
the  series.    The  shrinkage  of  the  selected  sets  is  49.9  %. 


128  HODGE.  [Vol.  VII. 


S  .-2 


o  .a 

S  S 

O  tn 

^  o 


TABLE  VIII. 

Stronger  Stimulation  and  Shorter  Rest  Interval, 

No. 

of  nuclei 

Mean 

Volume 

Time.          measured. 

diameter. 

shrinkage 

Cat  No.  9  (45  seconds'  rest 

to  15  seconds'  work) 2  hrs. 

100 

12.39 

I0.4S 

40.9  0/0 

Cat  No.    10   (intervals   15 

seconds'  rest  to   15   sec- 

onds' work) 2   " 

IOC  (T.) 

13-82 

12,04 

32.7  % 

2      I 

Two  facts  are  apparent.  First,  with  stronger  stimulation, 
naturally  enough,  the  effect  may  be  produced  in  two  hours  that, 
with  slight  stimuli,  it  required  ten  hours  to  obtain.  Second,  the 
length  of  rest  intervals  is  of  great  importance.  Although 
No.  10  received  exactly  twice  as  much  stimulation  in  the  two 
hours,  the  cells  show  considerably  less  change  than  those  of 
No.  9. 

Stimulation  has  brought  out  a  functional  differentiation  of 
some  sort  between  the  large  and  small  cells  of  the  spinal 
ganglia.  The  large  cells  show  the  effects  of  work  ;  the  snjiall 
cells  very  little,  or  not  at  all.  The  fact  is  too  well  marked  to 
pass  by  unnoticed. 

Considering  all  cells  large  which  have  one  diameter  50  yu.,  or 
over,  and  those  small  which  have  not,  a  count  gives  the  follow- 
ing result :  — 

Cat  No,  ii.  —  First  Thoracic  Ganglia. 

In  100  large  cells  nuclei.  In  loo  small  cells  nuclei. 

Shrunken.  Not  shrunken.  Shrunken.  Not  shrunken. 

Resting 5  95  o  100 

Stimulated 94  6  8  92 

A  few  fibres  going  to  a  ganglion,  the  vertebral  branch,  etc., 
escape  stimulation  by  our  method.  This  accounts  for  the  few 
large  cells  which  do  not  appear  worked  in  the  stimulated 
ganglion.  It  cannot  account  for  the  multitude  of  small  cells, 
comprising  numerically  more  than  half  the  cells  of  the  ganglion, 
which  do  not  show  the  effects  of  stimulation.  After  some 
searching,  a  field  was  found  (PI.  VII,  Fig.  2)  in  which  every 
nucleus  was  shrunken  ;  but  I  am  now  free  to  confess  that  only 
short-sighted  judgment  led  to  its  selection  for  the  plate.  No 
difference  between  the  cells  other  than  size  is  discernible. 


No.  2.]  CHANGES  IN  NERVE  CELLS.  1 29 

Regrets  come  always  too  late ;  and  so,  only  after  the  work 
had  been  done,  the  long,  tedious  measurements  completed,  and 
the  results  footed  up,  did  I  notice  how  widely,  in  point  of  size, 
the  cells  of  one  cat  differ  from  those  of  another  (compare  cats  6 
and  11),  and  wish  that  I  had  weighed  the  cats.  Cats  6  and 
9  were  females,  and  small.  However,  the  question  as  to  whether 
the  size  of  animals  of  a  species  differ  by  the  size  or  number  of 
cellular  elements,  or  both,  is  not  entirely  germane  to  our  sub- 
ject. Gaule^  would  maintain  that  for  any  species  the  number 
of  cells  is  a  constant,  variations  of  size  to  be  accounted  for  by 
size  of  cells.  Such  a  wide  variation  in  the  size  of  cells  as  is 
here  seen  favors  this  view. 

Many  devices  were  employed  to  eliminate  the  personal  equa- 
tion and  obtain  mechanical  measurements.  Three  persons  un- 
acquainted with  the  methods  of  the  research  kindly  consented 
to  assist  in  the  work  of  measuring.  Even  here  the  differences 
are  too  plain  to  make  an  absolutely  neutral  state  of  mind  long 
possible,  since  each  of  the  three,  before  completing  the  meas- 
urement of  a  single  set,  had  noticed  that  the  nuclei  in  the  two 
ganglia  were  different.  In  my  own  measurements,  I  was  wont, 
from  the  first,  to  throw  all  thought  of  the  work  as  completely  as 
possible  off  my  mind,  to  think  about  something  else,  to  have  an 
interesting  story  read  aloud.  In  general,  also,  all  the  measure- 
ments of  a  series  were  made  before  any  results  were  footed  up, 
so  that  the  way  they  were  tending  could  have  no  unconscious 
influence. 

This  laborious  and  time-consuming  method  of  treating  the 
sections  has  been  adopted  in  order  to  gain  some  slight  mathe- 
matical hold  directly  upon  the  working  of  the  nerve  cell.  It  is, 
however,  inadequate  to  express  the  facts  of  the  case,  and  it  is  at 
best  but  a  poor  expression  of  the  amount  of  change.  In  the 
first  place,  it  is  impossible  to  measure  accurately  the  jagged 
outline  of  a  worked  nucleus.  Our  practice  has  been  to  measure 
well  out  toward  the  tips  of  the  irregular  points  into  which  the 
nucleus  is  prolonged ;  and  this  would  tend,  evidently,  to  make 
the  computed,  larger  than  the  actual  volume.  In  the  second 
place,  the  quantities  in  the  tables  are  averages ;   whereas,  for 

1  Gaule,  Justus,  Zahl  unci  Verteilung  der  Markhaltigen  Fasern  im  Froschriick- 
enmark.  Abhanfll.  ri.  Math.-phys.  cl.  d.  k.  Sachs.  Geselhch.  d.  IVissensc/i.,  Bd.  XV., 
No.  9,  pp.  739-780.     1889,  Leipzig. 


I30 


HODGE.  [Vol.  VII. 


our  study,  exUrmes  are  naturally  of  more  interest.  The  ideal 
would  be  to  follow  a  living  nerve  cell  during  stimulation  from 
the  normal  resting  state  to  the  condition  of  extreme  fatigue. 
This  I  have  not  succeeded  in  doing  to  entire  satisfaction  as  yet. 
But  it  is  possible,  in  the  study  of  a  section,  to  find  a  fairly  good 
substitute  for  the  ideal.  We  see  some  cells  which  are  not 
affected  at  all ;  and  this  we  should  expect,  because  it  is  impos- 
sible to  stimulate  all  the  fibres  going  to  a  ganglion  without 
cutting  so  close  as  to  endanger  its  blood  supply.  Next,  we  find 
cells  that  are  slightly  worked.  In  the  even  outline  of  their 
nuclei  there  may  be  here  and  there  a  slight  indentation,  and  the 
nucleus  may  stain  a  shade  darker ;  now  and  then  a  small 
vacuole  makes  its  appearance  in  the  cell  protoplasm.  These 
nuclei  may  have  shrunken  five  or  ten  per  cent.  And  so  we 
pass,  by  all  degrees  of  difference,  to  cells  which  show  extreme 
fatigue.  And  here  the  protoplasm  is  riddled  with  vacuoles,  and 
the  nucleus  has  shrunken  to  a  densely  staining  speck,  which 
must  have  lost  seventy-five  to  eighty  per  cent  of  its  original 
volume. 

I  may  close  this  section  with  the  concluding  sentences  of  a 
former  paper.  We  have,  then,  "  as  a  result  of  electrical  stimu- 
lation :  — 

"y4.  For  the  nucleus  :  i.  Marked  decrease  in  size.  2.  Change 
from  a  smooth  and  rounded  to  a  jagged,  irregular  outline. 
3.  Loss  of  open  reticular  appearance  with  darker  stain, 

"^.  For  the  cell  protoplasm:  i.  Slight  shrinkage  in  size. 
2.  Lessened  power  to  stain  or  to  reduce  osmic  acid,  3,  Vacuo- 
lation. 

"  C.  For  the  cell  capsule :  Decrease  in  size  of  the  nuclei " 
(24,  p.  397). 

V.  Process  of  Recovery  from  Fatigue. 

At  the  point  in  the  investigation  reached  at  the  close  of  the 
last  section,  the  objection  was  raised  that  just  such  appearances 
had  long  been  known  to  occur  in  pathological  conditions  of  the 
nervous  system.  It  is  true  that  they  resemble  changes  hitherto 
described  as  pathological ;  but  up  to  the  present  no  attempt  has 
been  made  to  distinguish  changes  due  to  fatigue  from  those 
caused  by  disease,  and  on  a  priori  grounds  we  should  expect 


No.  2.]  CHANGES  IN  NERVE  CELLS.  131 

the  phenomena  of  fatigue  to  precede  and  shade  into  those  of 
disease. 

Several  facts  connected  with  the  research  negative  the  objec- 
tion ;  none,  not  even  the  so-called  pathological  appearance  of 
the  cells,  give  it  any  real  support.  In  the  first  place,  no  patho- 
logical factor,  capable  of  affecting  the  spinal  ganglia,  has  been 
introduced  into  the  experiments.  Electrical  stimulation  is  kept 
within  physiological  limits,  as  shown  by  the  fact,  that  the  nerves 
conduct  impulses  to  their  muscles  throughout  the  experiment. 
And  most  of  all,  the  fact,  that  the  change  increases  steadily  in 
amount,  as  stimulation  is  prolonged  or  intensified,  would  indicate 
that  we  are  dealing  with  normal  processes  of  the  active  living 
cell. 

But  aside  from  considerations  of  a  pathological  nature,  the 
process  of  recovery  in  a  tissue  has  an  interest  of  its  own,  physio- 
logical and  hygienic,  in  no  degree  less  than  that  which  attaches 
to  the  process  of  fatigue  itself.  The  bearing  of  the  literature 
upon  this  point  has  already  been  discussed.  We  know  that 
the  cells  of  the  epidermis,  from  which  the  nerve  cells  are  phylo- 
genetically  derived,  are  worn  out  and  off  and  are  replaced  by 
new  cells  produced  by  multiplication.  This  is  doubtless  true  of 
all  stratified  epithelia,  lining  surfaces,  internal  as  well  as  external. 
But  in  all  these  instances  we  have  friction  and  contact  with 
foreign  or  irritating  substances,  the  half-masticated  food  forced 
through  the  narrow  oesophagus,  dry  air  passing  rapidly  in  the 
trachea,  and  urine  in  ureters  and  bladder.  Friction  we  have  in 
the  blood-vessels ;  but  who  has  ever  found  epithelial  scales  in 
the  blood  such  as  occur  in  urine  or  in  saliva .-' 

From  what  is  known  of  the  structure  and  development  of  the 
nervous  system,  the  gradual  growth  of  the  nerve  fibre  from  the 
cell,  the  length  of  time  required  for  the  regeneration  of  a 
divided  nerve,  the  lack  of  any  evidence  of  fatigue  in  a  nerve, 
etc.,  it  would  seem  as  absurd  to  suppose  that  the  nerve  ele- 
ments die  out  and  are  replaced  as  to  advocate  the  daily  destruc- 
tion and  rebuilding  of  the  world's  telegraphic  systems.  Cables 
and  wires  and  keys,  accidents  aside,  are  practically  permanent ; 
and  so  are  the  battery  cells,  the  zincs  and  acids  alone  requiring 
renewal.  So  that  if  it  were  proven  that,  after  stimulation,  the 
cells  of  a  spinal  ganglion  fail  to  recover,  i.e.  die  out,  and  are 
replaced  by  new  cells,  I  should  be  free  to  admit  that  a  pathologi- 


132 


HODGE.  [Vol.  VII. 


cal  condition  had  been  induced,  rather  than  suppose  that  this 
were  the  normal  daily  procedure. 

To  study  recovery,  then,  it  was  arranged  to  stimulate  a  series 
of  cats,  equally  and  for  the  same  period,  and  then  allow  members 
of  the  series  to  rest  for  different  lengths  of  time. 

The  most  perfect  apparatus  for  controlling  stimulation  were 
supplied  me  by  the  physical  and  physiological  laboratories  of 
Clark  University,  A  Weston's  direct  reading  ammeter,  read- 
ing from  0-15  amperes,  was  placed  next  the  battery.  From 
this  it  was  possible  to  read  off  the  strength  of  current  at  any 
moment.  Next  to  this  in  the  circuit  was  placed  a  resistance- 
box  with  rheocord  attached.  This  is  necessary  for  exact  work, 
as  the  battery  was  set  fresh  at  the  beginning  of  each  experi- 
ment and  increased  in  power  for  the  first  hour  or  so,  and  then 
gradually  weakened  until  the  end  of  five  hours,  during  which 
the  stimulation  lasted.  These  variations  could  generally  be 
compensated  for  by  sliding  the  bridge  of  the  rheocord. 

It  was  decided  to  use  twenty  stimuli  per  second,  and  this  rate 
was  obtained  by  loading  the  interrupting  hammer  attached  to 
the  induction  coil.  To  make  certain  that  this  did  not  jar  out  of 
adjustment,  I  was  compelled  to  place  also  in  the  primary  circuit 
a  signal  which  should  write  its  vibrations  under  the  tracing  of 
a  signal  in  circuit  with  a  seconds  clock. 

The  same  interval  was  adopted  as  for  the  last  series,  viz.  forty- 
five  seconds'  rest  alternating  with  fifteen  seconds'  stimulation.  I 
am  indebted  to  Dr.  Lombard  for  the  most  inexpensive  and  ser- 
viceable little  device  ever  invented  for  the  spacing  of  intervals. 
A  small  nickel  clock  forms  the  motor  part  of  the  contrivance.  It 
must  be  provided  with  a  second  hand.  The  glass  face-cover 
and  all  the  hands  are  removed,  and  upon  the  shaft  of  the  second 
hand  is  fastened  an  eccentric  zinc  disc  2i  x  3  cm,  in  diameter. 
In  front  of  the  clock  is  held  by  a  post,  properly  placed,  a  lever 
of  hard  rubber  1 5  cm.  in  length ;  the  longer  arm  of  the  lever, 
8  cm.,  is  between  the  post  and  the  clock,  so  that  this  end,  which 
is  tipped  with  a  small  gutta-percha  wheel,  to  reduce  friction,  will 
tilt  back  lightly  upon  the  eccentric.  The  other  arm  of  the  lever 
carries  two  light  copper  wires  tipped  with  platinum.  The  plati- 
num tips,  extending  downward  at  right  angles  from  the  lever, 
dip  into  a  glass  mercury-cup.  Thus  the  motion  of  the  eccentric 
upon  the  second  shaft  is  made  to  tilt  the  lever  in  and  out  of  the 


No.  2.]  CHANGES  /AT  NERVE  CELLS.  133 

mercury  every  minute.  By  placing  the  cup  upon  the  head  of  a 
screw,  so  that  the  mercury  can  be  raised  and  lowered  at  will, 
and  by  proper  shaping  of  the  eccentric  disc,  it  is  easy  to  so 
adjust  it  that  the  circuit  is  made  through  the  mercury  fifteen 
seconds  and  broken  forty-five  seconds,  which  is  the  spacing  of 
intervals  desired.  The  whole  is  arranged  upon  a  small  board, 
into  which  two  binding  screws  are  set  for  convenience  of  joining 
up  with  the  circuit.  This  is,  of  course,  placed  in  the  primary 
circuit. 

By  this  arrangement  it  was  possible  to  control  stimulation 
quite  accurately.  A  half  ampere,  as  read  from  the  galvanometer, 
was  used  throughout  the  series.  The  automatic  make  and 
break  key  gave  regular  intervals  of  rest  and  stimulation.  The 
beat  of  the  interrupter  was  kept  at  twenty  per  second.  The 
secondary  coil  was  set  at  a  certain  place  and  moved  up  at  regu- 
lar intervals,  in  the  same  manner  for  all  the  experiments. 

The  animals  used  were  a  lucky  lot,  five  gray  kittens  six  or 
eight  weeks  old,  and  as  much  alike  as  peas  in  a  pod.  Nothing 
was  fed  after  the  commencement  of  the  experiment,  but  up  to 
that  time  they  were  so  well  fed  that  it  was  thought  a  fast  of 
eleven  to  thirty  hours  would  not  complicate  matters  seriously, 
if  at  all.  The  operation  was  made  in  every  respect  according  to 
the  description  already  given.  Stimulation  was  continued  for 
five  hours  in  each  case.  The  animal  was  then  gently  removed 
from  the  holder,  wrapped  up,  and  laid  in  a  warm  place,  where  it 
was  left  to  sleep  the  desired  number  of  hours.  At  the  expira- 
tion of  this  time  the  ganglia  were  cut  out  as  quickly  as  possible. 
The  1st  thoracic  and  8th  cervical  pairs  were  used  and  were  hard- 
ened respectively  in  one  per  cent  osmic  acid  and  saturated 
mercuric  chloride  solution  of  40°  C.  The  precautions  regarding 
exactly  similar  treatment  were  the  same  as  described  for  the 
preceding  series,  and  the  cells  and  nuclei  were  measured  and 
dealt  with  by  the  method  of  arithmetical  means  as  before. 

As  there  is  often  reason  to  distrust  averages,  I  will  give  the 
actual  figures  as  they  occur  in  a  sample  sheet  of  my  notes 
taken  at  random.  The  measurements  were  made  with  a  Zeiss 
eye-piece  micrometer  ruled  to  |  micron  divisions  (eye-piece  8 ; 
objective  4.0  mm.  x  500),  hence  each  division  equals  2|ytA.  They 
are  given,  as  read,  in  units  of  the  micrometer. 


134 


HODGE. 


[Vol.  VII. 


Cat  No.  17.  —  Measurement  of  Diameter  of  Nuclei. 


Right.  — After  s  hrs.  stimulation  and 
o  hrs.  rest. 

Number  of 
Diameter.  measurements. 

8.5 3 

8 I 

7-5 4 

7 17 

6.5 17 

6 48 

5.5 .^ 

5 44 

4-5 14 

4 17 

3-5 4 

3 ^ 

200 

Average  diameter  for  set,  5.39. 


Left.  —  Normal. 


Number  of 
Diameter.  measurements. 

9 3 

8.5 6 

8 28 

7-5 17 

7. ^ 

"6^5 ^ 

6 33 

5-5 12 

5 :}}_ 

200 


Average  diameter  for  set,  6.83. 


The  above  is  sufficient  to  show  that  the  mean  of  these  diam- 
eters is  a  fair  average.  The  measurements  stand  in  about  equal 
numbers  above  and  below  it  in  both  cases.  The  largest  nuclei 
are  found  among  the  normal  cells  and  the  smallest  among  the 
stimulated  cells. 


No.  2.] 


CHANGES  IN  NERVE  CELLS. 


135 


The  results  of  the  whole  series  may  be  seen  at  a  glance  from 

the  following  table  :  — 

TABLE   IX. 

Series  to  show  Influence  of  Rest. 

Right  brachial  plexus  of  each  stimulated  in  the  same  manner  for  five  hours, 
and  allo^ved  to  rest. 


Nuclei. 

Cells. 

Rest. 

Mean  diameter  of  nucleus 
in  /u.. 

Shrinkage. 

Meandiam. 
in  ij.. 

Cat  17 

0  hrs. 
6.5  hrs. 
12  hrs. 
18  hrs. 
24  hrs. 
Normal. 

16.40  Left,  normal. 
12.93  Right,  stimulated. 

16.70  Left,  normal. 
15.09  Right,  stimulated. 

16.34  Left,  normal. 
14.73  Right,  stimulated. 

17.08  Left,  normal. 
16.03  Right)  stimulated. 

17.01  Left,  normal. 

1 7. 1 1  Right,  stim  ulated. 

14.20  Left. 
14.54  Right. 

48.8  % 

26  0/0 

26% 

18% 

+  2% 

+  6.9  % 

57 

Cat  16 

52 
56 

Cat  21 

54 
55 

Cat  19 

51 
56 

Cat  18 

55 

From  Table  VII. 

Cat    7 

In  this  series  stimulation  was  severe  ;  but  it  must  be  remem- 
bered that  during  the  so-called  five  hour  period  of  work  it  was 
applied  for  only  fifteen  seconds  each  minute.  Five  hours  of 
stimulation  represent,  therefore,  only  one  hour  and  a  quarter 
active  working  of  the  cells.  In  this  short  time  the  change  is 
marked  as  shown  by  a  shrinkage  of  48.8  per  cent  in  the  nuclei 
of  the  stimulated  side.  The  cells,  as  before,  shrink  little,  and 
the  cell  protoplasm  exhibits  considerable  vacuolation.  (For 
effect  of  five  hours'  stimulation,  cat  17,  compare  Fig.  i  with  Fig. 
2,  and  Fig.  3  with  Fig.  4.  For  influence  of  rest,  cats  16  and  17, 
compare  Fig.  5  with  Fig.  4  and  with  Fig.  3,  PI.  VII.)  This,  as 
before  remarked,  is  not  well  shown  in  the  plate.  In  general, 
substance  is  lost  from  the  cell  interstitially  as  shown  by  vacu- 
oles and  lighter  granulation,  while  the  nucleus  collapses  bodily. 
This  would  seem  to  indicate  that  the  reticulum  of  the  cell  pro- 
toplasm is  stiff  and  elastic  enough  to  hold  its  shape  when  the 


136  HODGE.  [Vol.  VII. 

interfibrillar  substance  is  removed,  whereas  that  of  the  nucleus 
is  too  soft  or  delicate  to  resist  the  pressure  of  the  lymph 
about  it. 

The  ideal,  in  following  the  process  of  recovery  in  a  nerve  cell, 
would  be  to  watch  continuously  a  living  active  cell  for  the 
required  length  of  time.  For  the  present,  however,  we  have 
only  specimens  prepared  by  two  good  methods,  taken  so  as  to 
give  us  presumably  five  steps  in  the  process. 

As  before  remarked,  the  table  gives  but  a  meagre  notion  of 
the  facts.  The  processes  of  recovery  are,  in  general,  the  reverse 
of  those  of  fatigue.  The  nucleus  and  protoplasm  gradually 
return  to  normal  appearance.  The  protoplasm  seems  to  recover 
rapidly.  At  any  rate,  in  the  specimen  which  has  rested  six  and 
one-half  hours,  little  trace  of  vacuolation  is  observable  ;  and  this 
is  true  of  all  those  which  have  rested  for  a  longer  time.  The 
nuclei,  on  the  other  hand,  recover  slowly.  After  six  and  one- 
half  hours'  rest  they  show  a  marked  gain  in  size,  but  still  retain 
the  dense  stain  characteristic  of  fatigue.  Indeed,  in  this  respect 
the  process  of  recovery  is  not  entirely  completed  in  all  the  nuclei 
which  have  rested  for  twenty-four  hours,  it  being  still  possible  to 
find  a  few  large  but  densely  stained  nuclei.  So  far  as  it  goes,  my 
observations,  therefore,  favor  the  view  that  granules  arise  within 
the  nucleus  in  some  peculiar  manner,  although  in  a  nerve  cell 
they  are  too  small  and  ill-defined  by  any  method  I  have  used  to 
permit  of  seeing  the  manner  of  their  migration  into  the  cell  pro- 
toplasm, if,  indeed,  any  such  thing  takes  place, 

A  study  of  nerve  cells,  thus,  after  long  periods  of  complete 
rest,  has  brought  out  a  point  of  general  interest  to  the  histology 
of  the  nervous  system.  An  appearance  often  noted  in  nerve 
histology  has  hitherto  complicated  all  of  our  experiments.  This 
is  the  fact  that  individual  cells  in  the  same  ganglion  present  such 
great  histological  differences.  Ranvier^  calls  attention  to  this 
fact  and  proves  that  it  cannot  be  due  to  the  action  of  reagents, 
but  must  express  some  difference  between  the  cells  themselves. 

1  Ranvier,  Traite  U Histologie,  Paris,  1889,  p.  802 :  "  How  is  it  that  a  little  gan. 
glion,  placed  in  a  solution  of  ammonium  bichromate,  all  the  elements  of  which  are 
therefore  submitted  to  the  same  influences,  contains,  side  by  side,  cells  modified  in  a 
manner  so  widely  different?  This  is  a  fact  which  we  cannot  yet  explain,  but  upon 
which  we  must  insist,  because  we  see  it  repeated  in  the  spinal  cord,  the  cerebrum, 
the  cerebellum,  etc.;   that  is  to  say,  in  all  organs  containing  ganglion  cells." 


No.  2.]  CHANGES  IN  NERVE  CELLS.  137 

In  my  own  experiments,  even  in  sections  of  normal,  resting  gan- 
glia, I  invariably  find  a  few  cells  which  have  all  the  appearances 
of  being  worked.     The  number  of  these  cells  in  normal  ganglia 
varies,  but  may  reach  five  to  ten  per  cent,  while  in   stimulated 
ganglia  they  often  exceed  ninety  per  cent.     My  theory  was 
in  such  cases  that  some  of  the  cells  had  become  more  or  less 
fatigued   by  the  ordinary  activity  of   the  animal.      This   was 
merely  supposition.      It  might  also  have  been   supposed  that 
these  cells  were  in  process  of  degeneration.     But  after  we  have 
wrapped  up  an  animal  in  cotton  batting  and  laid  it  in  a  warm 
chamber  at  constant  temperature  for  twenty-four  hours,  its  brain 
having  been  previously  destroyed,  so  that  it  makes  no  voluntary 
movements,  after  scarcely  a  sensory  impulse  has  broken  the  rest 
of  the  cells  for  that  length  of  time,  we  find,  as  might  be  expected, 
all  the  cells  in  most  perfect  resting  condition.    The  cells  appear 
uniformly  full,  with  not  a  single  shrunken  nucleus  visible.     The 
nuclei,  in  fact,  appear  larger,  rounder,  and  clearer  than  in  any 
specimen  I  have  hitherto  examined.     It  would  seem,  therefore, 
quite   possible    that   the    differences    between    ganglion    cells, 
observed  in  sections  of  the  same  specimen,  may  be  due  to  the 
phase  of  functional  activity  or  of  nutrition  in  which  each  of  the 
cells  happened  to  be  when  it  died  or  was  killed  by  the  reagent. 

No  one  is  better  aware  than  the  writer  that  repetition  of  such 
a  series  of  experiments  is  desirable.  My  time  and  work,  how- 
ever, did  not  permit  of  this  ;  and  it  was  thought  preferable  that 
some  one  else  should  be  allowed  to  make  the  repetition,  in  case 
these  experiments  are  not  considered  conclusive.  Everything 
in  the  work  has  been  made  as  exact  and  mathematical  as  possi- 
ble, on  the  one  hand,  in  order  to  do  away  with  the  necessity  for 
repetition,  and,  on  the  other,  to  make  exact  repetition  possible. 
As  far  as  the  specimens  obtained  from  the  series  are  con- 
cerned, they  leave  no  room  for  questioning  the  two  following 
conclusions  :  — 

First,  that  spinal  ganglion  cells  of  kittens  do  recover  from  the 
effects  of  electrically  stimulating  the  nerve  going  to  them. 

Second,  that  recovery  may  be  a  slow  process.  It  is  not  com- 
plete after  eighteen  hours,  but  is  found  to  be  about  complete 
after  a  rest  of  twenty-four  hours. 

Pre-eminently  master  among  the  tissues  of  the  animal  body, 
controlling  their  activity  in  so  many  ways,  in  starvation  holding 


138  HODGE.  [Vol.  VII. 

its  own  by  the  tribute  rendered  to  it  even  by  muscle,  I  had 
expected  to  find  the  power  to  recover  much  more  energetic  in 
the  nerve  cell  than  in  gland  cells,  the  process  of  recovery  in 
which  has  received  some  attention  (on  this  point  see  39,  p.  587). 
No  attempt  to  draw  any  exact  time  parallel  between  the  action 
of  the  gastric  cells  of  a  frog  and  the  spinal  ganglion  cells  of  a 
kitten  is  to  be  understood  from  the  present  reference.  It  is, 
however,  of  interest  to  note  in  this  connection  that  Langley  and 
Sewall  found  that,  upon  feeding  a  frog,  the  granules  commenced 
to  pass  out  of  the  cells  of  the  stomach,  and  continued  to  do  so 
for  about  six  hours,  when  they  began  to  fill  up  the  cells  again, 
and  recovery  was  not  complete  until  twenty-four  hours  had 
elapsed  (34,  p.  676).  That  is,  to  recover  from  six  hours'  secre- 
tion required  twenty-four  hours'  rest.^ 

VI.    Curve  of  Nerve  Cell  Fatigue  and  Recovery. 

In  the  foregoing,  data  are  present  from  which  to  construct  a 
curve  that  may  provisionally,  at  least,  be  taken  to  represent  the 
process  of  fatigue  and  recovery  in  the  cells  of  the  spinal  gan- 
glia. Whether  these  results  are  applicable  to  the  action  of 
other  kinds  of  nerve  cells,  it  is  impossible  to  say  with  certainty. 
And  whether  the  action  of  the  nucleus  may  be  fairly  considered 
an  index  of  the  whole  process  is  open  to  question.  But  we 
have  shown  that  this  shrinkage  of  the  nucleus  is  directly  pro- 
portional to  the  duration  and  also  to  the  intensity  of  stimula- 
tion, and,  in  general,  inversely  proportional  to  the  length  of 
the  period  of  rest.  At  any  rate,  it  is  the  only  index  we  have  at 
present,  and  we  may  be  permitted  to  use  it  with  the  understand- 
ing that  the  curve  obtained  is  entirely  provisional. 

The  curve  of  fatigue  for  a  muscle  is  generally  described  as  a 
straight  line  which  falls  more  or  less  abruptly  according  to  its 
load,  and  the  strength  and  frequency  of  stimuli  applied  to  it. 
The  fatigue  of  a  muscle  in  situ  is,  moreover,  an  exceedingly 
slow  process  (39,  p.  547),  if  a  physiological  process  at  all.  Roth 
stimulated  muscles   continuously  for  as  long  as  twenty  days 

1  It  will  be  remembered  that,  if  a  frog  is  fed  a  piece  of  sponge  instead  of  a  worm, 
recovery  may  be  greatly  slowed.  In  another  series  of  experiments  I  shall  attempt 
feeding  regularly.  However,  Langley's  experiments  and  my  own  in  this  respect  are 
clearly  not  comparable,  since  sponge  acted  to  produce  a  much  longer  stimulation 
than  food. 


No.  2.] 


CHANGES  IN  NERVE  CELLS. 


139 


before  producing  complete  exhaustion.  The  fatigue  curve  of  a 
nerve  fibre  has  been  shown,  for  short  intervals  at  least,  to  be  a 
straight  line  which  remains  parallel  to  its  base  line;  i.e.  within 
physiological  limits  a  nerve  fibre  is  not  susceptible  of  fatigue 
(8;  9;  79;  40). 

No  curve  representing  fatigue  of  the  nerve  cell,  drawn  directly 
from  observation  of  the  cell  itself,  has  hitherto  been  made.  The 
nearest  approach  to  this  is  to  be  found  in  such  work  as  Mosso 
(54,  pp.  175,  185,  186)  and  Lombard  (44,  Figs.  3  and  5)  have 
done  for  the  fatigue  which  manifests  itself  in  voluntary  muscu- 
lar contractions  (Mosso,  see  plates  pp.  178,  185,  186;  Lombard, 
see  PI.  II,  Fig.  5).  If,  as  would  seem  demonstrated,  the  curve 
which  these  investigators  find,  expresses,  in  some  way,  the 
fatigue  of  the  brain  or  spinal  cord  cells,  we  may  say  that  the 
nerve  cell  tires  rapidly  at  first,  then  slowly,  or  possibly  gains  a 
little  or  holds  its  own  for  some  time,  and  at  last  falls  quite 
rapidly  again  to  a  state  of  complete  exhaustion.  It  is  not 
possible,  of  course,  to  say  whether  any  nerve  cell,  even  the 
most  shrunken  and  vacuolated  to  be  found,  has  been  entirely 
exhausted ;  probably  not ;  so  the  end  of  our  curve  will  not  be 
complete.  But  if  we  now  plot  the  percentages  given  in  table 
VII  for  a  fatigue  series,  we  find  a  curve  quite  similar  to  those 
obtained  by  Mosso  and  Lombard. 

We  have  from  the  table  slight  stimulation,  for  one  hour,  two 
and  one-half  hours,  five  hours,  and  ten  hours,  causing  a  shrink- 


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age  in  the  volume  of  the  cell  nucleus  of  respectively  22  percent, 
21  per  cent,  24.3  per  cent,  and  43.9  per  cent.  This  is  repre- 
sented to  the  eye  by  the  dotted  line  in  Fig.  i.  For  the  first 
hour  the  nuclei  shrink  rapidly,  for  three  or  four  hours  they 
almost    hold  their  own,  and    then    shrink  quite  rapidly  again. 


j^o  HODGE.  [Vol.  VII. 

How  much  I  was  chagrined  at  first  in  not  finding  the  curve  a 
straight  line,  Hke  that  for  the  fatigue  of  a  muscle,  I  will  not 
stop  to  say. 

Another  point  of  great  importance,  viz.  that  the  curve  of  Dr. 
Lombard,  just  referred  to,  was  obtained  from  but  a  few  minutes' 
work,  whereas  mine  represents  the  fatigue  of  ten  hours,  I 
cannot  discuss  in  full  until  my  work  upon  the  changes  in  the 
living  ganglion  cell  under  stimulation  is  completed.  It  will  be 
sufficient  for  the  present  to  remind  the  reader  that  the  dots 
showing  breaks  in  the  curve  at  one  hour,  two  and  one-half  hours, 
five  hours,  and  ten  hours  are  points  taken  in  an  entirely  arbi- 
trary manner.  Had  the  observations  been  made  every  hour,  or 
every  half-hour,  the  curve  might  have  passed  through  the  same 
points  and  at  the  same  time  have  been  materially  different.  In 
other  words,  there  is  no  reason  to  believe  that,  for  example,  just 
at  the  end  of  five  hours  fatigue  began  to  be  accelerated.  This 
point  may  have  occurred  in  reality  at  the  sixth,  seventh,  eighth, 
or  ninth  hour,  or  at  any  time  between.  That  is  to  say,  the 
points  of  the  curve  may  be  averages  of  wide  fluctuations  occur- 
ring between  them.  Clearly,  the  only  way  to  settle  this  point 
is  to  make  the  intervals  of  observation  much  closer  together, 
or,  as  I  hope  to  do  more  successfully  than  hitherto,  to  watch 
closely  the  living  cell  during  a  considerable  period  of  stimulation. 

By  the  continuous  line  in  the  figure  is  represented  the  proc- 
ess of  recovery  in  the  series  of  rest  experiments  (Table  IX), 
in  which  five  hours  of  severe  work  has  caused  a  shrinkage  of 
the  nuclei  of  48.8  per  cent,  recovery  taking  place  as  indicated 
by  the  second  part  of  the  curve.  The  curve  of  recovery,  in  this 
instance,  is  seen  to  rise  quite  rapidly  at  first,  then  more  slowly, 
and  again  more  rapidly  to  a  point  a  little  above  the  normal. 
This  is  the  exact  opposite  of  the  view  given  by  Landois  and 
Stirling  (39,  p.  587)  :  "  When  a  nerve  recovers,  at  first  it  does 
so  slowly,  then  more  rapidly,  and  afterward  again  more  slowly." 
However,  if  depth  of  sleep  may  be  taken  to  represent  rapidity 
of  recovery,  then  the  curve  given  by  Exner  (12,  p.  296)  for  depth 
of  sleep,  with  the  necessary  reconstruction,  corresponds  not  so 
badly  with  my  own  curve. 

It  is  not  strange  or  anomalous  that  the  curves  of  fatigue  and 
recovery  should  be  in  character  alike,  since  both  processes  must 
be  of  a  similar  nature.     That  is,  both  are  processes  of  the  liv- 


No.  2.]  CHANGES  IN  NERVE  CELLS.  141 

ing,  active  cell.  The  cell  is  perhaps  as  actively  at  work  in 
phases  of  anabolic  as  in  katabolic  changes.  Neither  is  it  anoma- 
lous that  these  changes  do  not  go  on  in  the  cell  continuously 
and  with  equal  steps.  Perhaps  no  instance  of  living  cells  work- 
ing thus  continuously  could  be  cited  in  all  biology.  Everything 
seems  to  be  done  in  rhythm.  And  if  the  cells  of  a  cleaving 
ovum  pass  through  "  resting  stages  "  and  "  stages  of  activity  "  ^ 
(83,  p.  292),  and  if  the  bodies  of  school  children,  as  Bowditch  2 
has  shown,  grow  not  continuously  and  equally,  but  now  fast 
and  again  more  slowly,  there  is  every  reason  to  suppose  that 
nerve  cells  may  follow  the  same  rule.  Thought,  psychologists 
tell  us,  flows  not  continuously,  but  in  waves.  And  general 
experience  proves  that  the  beat  of  the  waves  of  thought  is  not 
equable  and  uniform,  but  variable  in  the  extreme.  Now  they 
dash  high,  now  they  run  in  a  gentle  ripple,  now  there  is  the 
calm  of  stupidity  or  sleep.  And  may  not  thought  be  an  index 
to  the  activity  of  nerve  cells  .-* 

I  have  already  stated  that  these  curves  are  provisional.  In 
fact,  they  have  been  introduced  with  the  purpose  of  showing 
that  they  cannot  be  wholly  relied  upon,-  rather  than  of  attaching 
permanent  value  to  them.  This  is  because  an  important  factor 
in  their  shaping  has  been  entirely  ignored.  This  factor  is,  of 
course,  the  normal  tendency  toward  activity  or  toward  rest, 
toward  anabolism  or  toward  katabolism  present  in  the  cells 
while  the  stimulus  is  being  applied. 

From  the  first,  we  have  been  endeavoring  to  discover  only 
such  changes  as  occur  in  the  normal  functional  activity  of  the 
nerve  cell.  That  changes  already  described  do  relate  to  normal 
and  not  to  pathological  processes  seems  conclusively  proved. 
If,  then,  these  changes  are  normal,  there  should  be  no  difficulty 
in  demonstrating  a  similar  rhythmic  curve  of  rest  and  work  in 
the  normal  daily  activity  of  the  animal.  No  more  fundamental 
rhythm  exists,  either  in  physiology  or  psychology,  than  that  of 
activity  alternating  with  rest,  sleep  with  waking.  And  this 
rhythm,  from  such  work  as  Lombard  (45,  pp.  n  ff)  has  done, 

1  Ref.  W.  K.  Brooks'  "  Alternations  of  Periods  of  Rest  with  Periods  of  Activity 
in  the  Segmenting  Eggs  of  Vertebrates,"  Studies  Biol.  Laborat.,  Johns  Hopkins 
University,  Vol.  II.,  1882. 

2  H.  P.  Bowditch,  "The  Growth  of  Children,"  Mass.  State  Board  of  Health. 
Twenty-second  Annual  Report,  p.  509.     Boston,  1891. 


J  ^2  HODGE.  [Vol.  VII. 

showing  the  influence  of  sleep  upon  volitional  power,  must  be 
closely  connected  with,  if  not  entirely  dependent  upon,  events 
taking  place  in  the  central  nervous  system. 

If  any  such  rhythm  exists  in  the  cells  of  the  spinal  gangha, 
it  is  evident  that  such  curves  as  we  have  drawn  may  be  pro- 
foundly influenced  by  it.  A  stimulation  of  five  or  ten  hours  is 
physiologically  a  trivial  matter  compared  with  a  fundamental 
rhythm  which  has  become  through  generations  an  established 
fact  in  the  economy  of  an  animal  species ;  and  if  the  changes 
in  such  a  rhythm  are  similar  to  those  which  have  been  demon- 
strated by  means  of  artificial  stimulation,  then  clearly  the  effects 
in  each  case  have  been  resultants  between  the  influence  of 
stimulation  and  the  tendency  of  the  animal's  rhythm  at  the 
time.  That  is,  if  stimulation  be  applied  while  the  animal's 
curve  is  falling  most  rapidly  into  sleep,  we  should  not  expect  the 
same  effect  which  would  be  obtained  were  the  animal's  curve  of 
nervous  activity  on  the  rise, 

A  young  dog  stimulated  severely  for  ten  hours,  from  5.30  p.m. 
until  3.30  A.M.,  showed  scarcely  a  trace  of  fatigue.  The  purpose 
of  the  experiment  was  by  no  means  to  illustrate  the  point  under 
discussion,  but  to  obtain  the  greatest  amount  of  change  possible 
in  the  spinal  ganglion  cells.  The  result,  at  the  time,  struck 
consternation.  Facts  which  it  was  hoped  were  of  general  appli- 
cation, fitting  equally  well  the  activity  of  nerve  cells,  wherever 
found,  in  the  animal  series  from  the  highest  to  the  lowest,  must 
now  be  given  most  absurd  limitations.  This  and  this  is  true 
for  the  spinal  ganglion  cells  of  a  frog  or  cat,  but  not  for  the 
same  cells  of  a  dog,  and  may  or  may  not  be  true  for  man  or 
any  other  animal.  The  shock  of  this  unexpected  result  was 
paralyzing  at  first ;  and  whether  we  are  justified  in  saying  that 
the  tendency  toward  recovery,  the  tendency  to  sleep,  in  the 
cells  of  the  spinal  ganglia  was  strong  enough  to  counterbalance 
an  intense  stimulus,  which  was  sufficient  to  cause  constant 
and  vigorous  contractions  of  the  muscles  supplied  by  the 
stimulated  nerve,  is  doubtful,  and  plainly  requires  further 
experiment  to  decide.  This  seems  to  be,  however,  the  simplest 
explanation  of  the  phenomenon  at  present.  And  in  saying 
this,  the  writer  is  fully  aware  that,  more  than  two  hundred 
years  ago,  Swammerdam  studied  reflex  action  in  sleeping  ani- 
mals and  men,  and  hence  that  the  cells  of  the  reflex  arc  must 


No.  2.]  CHANGES  IN  NERVE  CELLS.  1 43 

be  somewhat  irritable  in  sleep  ^  (43,  p.   53  ;  58,  p.   345  ;  39,  p. 

693)- 

A  second  dog,  stimulated  similarly  for  one  hour  and  twenty- 
five  minutes  {10.05  to  11.30  a.m.),  dying  suddenly  from  the  oper- 
ation on  the  brain  at  the  end  of  this  time,  showed  most  clearly 
the  characteristic  effects  of  fatigue.  Hence,  we  are  not  com- 
pelled to  make  an  exception  in  the  case  of  dogs. 

It  is  plain  from  the  above  considerations  that  a  study  of  the 
normal  rhythm  of  sleep  and  activity  should  be  made  for  the 
animal  employed  in  connection  with  further  work  of  this  kind. 
To  this  end  I  have  kept  under  constant  observation  for  a  week 
a  half-grown  kitten  similar  to  the  ones  used  in  my  experiments. 
The  sleep  of  such  a  kitten  depends  largely  upon  the  amount  of 
food  given  to  it.  If  fed  to  repletion,  it  would  sleep  as  much 
as  eighteen  hours  a  day,  and,  even  when  sparingly  fed,  slept 
twelve  and  one-half  or  thirteen  hours.  It  seemed  to  be  able  to 
sleep  equally  well  day  or  night.  In  short,  the  curve  of  nervous 
activity  of  a  cat  is  most  irregular. 

It  will  be  noted  that  if  the  cat  possesses  no  marked  daily 
rhythm  of  rest  and  activity,  our  provisional  curves  are  more 
likely  to  be  correct. 

VII.    Effects  of  Normal  Daily  Fatigue. 

A  crucial  test  as  to  the  value  of  foregoing  experiments  for 
normal  physiology  is  readily  seen  to  lie  in  the  question.  Do 
changes  in  ganglion  cells,  like  those  observed  during  artificial 
stimulation,  actually  occur  in  the  normal  activity  of  an  afiintal  ? 
If  they  do  not,  the  experiments  do  not  concern  normal  physi- 
ology of  the  nervous  system.  In  spite  of  all  proof  to  the  con- 
trary, they  must  be  considered  pathological.  If  they  do  occur, 
with  the  evidence  already  adduced,  it  will  be  but  fair  to  consider 
them  a  part  of  the  normal  physiological  activity  of  the  nervous 
system. 

*  This  experiment  may  have  been  further  complicated  by  the  fact  that  the  pup, 
being  of  large  breed  and  growing  rapidly,  lymph  in  great  amount  exuded  from  the 
wound  and  formed  a  pool  in  the  axilla  around  the  nerves  and  electrode.  I  did 
not  notice  this  until  quite  late,  when  I  thought  that  the  contractions  were  becoming 
weak  from  fatigue.  On  wiping  up  the  lymph  more  carefully,  they  became  as  strong 
as  at  first.  In  short,  stimulation  may  not  have  been  as  "  intense  "  as  I  had  designed 
to  have  it. 


144 


HODGE.  [Vol.  VII. 


A  number  of  considerations  combine  to  create  a  strong  pre- 
sumption in  favor  of  the  supposition  tliat  these  changes  will  be 
found  in  normal  activity.  The  processes  in  a  gland  have  been 
found  to  be  identical,  whether  produced  by  artificially  stimu- 
lating the  nerve  going  to  it  or  by  the  normal  stimulus  of  food. 
Electrical  stimulation  of  a  nerve  causes  contraction  of  muscle 
exactly  similar  to  that  produced  by  a  normal  nerve  impulse. 
And  here  we  have  the  normal  impulse  producing  a  stronger 
contraction  than  an  electrical  stimulus.  If  the  same  law  holds 
good  for  centrally  as  for  peripherally  passing  impulses,  for  sen- 
sory as  for  motor  impulses,  we  should  find  a  greater  effect  in 
sensory  cells  due  to  the  normal  stimuli  of  the  animal's  life  than 
we  are  able  to  cause  by  stimulating  an  exposed  nerve  trunk. 
But,  most  of  all,  the  phenomena  of  daily  fatigue,  so  closely  con- 
nected with  the  central  nervous  system,  with  the  absolute  neces- 
sity of  not  only  rest  but  of  long  continued  sleep  for  recovery  of 
nervous  power,  is  inexplicable  on  any  ground  which  does  not 
suppose  profound  changes  within  the  central  nervous  system  ; 
and,  knowing  what  we  do  as  to  the  fatigue  of  nerve  fibres,  we 
may  place  these  changes  within  the  nerve  cells  themselves. 

If  normal  daily  fatigue  is  to  be  studied,  first  of  all  it  is  neces- 
sary to  choose  an  animal  in  which  a  diurnal  rhythm  of  rest  and 
activity  is  highly  developed.  The  cat  we  know  is  not  such 
an  animal,  although  the  cat  or  other  laboratory  animals  might 
be  employed  under  the  compulsion  of  some  sort  of  exercising 
machine,  and  this  may  be  done  later.  For  the  present,  we  wish 
distinctively  to  avoid  all  compulsion  and  to  study  only  such 
activity  as  an  animal  normally  and  voluntarily  puts  forth  in  the 
ordinary  round  of  its  daily  life. 

In  no  animals  is  this  daily  rhythm  more  constant  than  in  day 
birds  and  insects.  In  both  of  these  classes,  too,  metabolic 
changes  are  known  to  be  vigorous  and  rapid.  The  work  done 
in  a  day  by  certain  kinds  of  birds  or  insects  is  enormous,  and 
could  probably  not  be  equalled,  per  body  weight,  by  animals  of 
any  other  group. 

Method. 

In  a  former  communication  (24,  p.  331)  the  words  occur,  "It 
was  found  that  the  ganglion  cells  of  two  frogs  that  could  not 
be  distinguished  externally  might  differ  widely  in  staining  and 


No.  2.]  CHANGES  IN  NERVE  CELLS.  145 

general  appearance."  Probably  the  same  statement  holds  good 
for  individual  birds  and  bees.  Nevertheless,  we  are  compelled 
to  abandon  this  safe  precaution  of  using  only  cells  from  differ- 
ent sides  of  the  same  animal.  It  would  be  clearly  impossible 
to  remove  a  spinal  ganglion  from  one  side  of  a  bird  or  one  half 
of  a  bee's  brain  in  the  morning  and  the  corresponding  parts  at 
night,  without  seriously  interfering  with  the  animal's  normal  ac- 
tivity. Nothing  of  the  sort  was  attempted.  However,  wherein 
the  rigidity  of  the  method  is  weakened  by  comparison  of  the 
cells  of  different  animals,  it  is  possible  to  strengthen  it  by  mak- 
ing observations  more  numerous. 

Aside  from  this  the  method  of  operation  is  essentially  the 
same  as  that  already  described.^  The  birds,  sparrows  and  swal- 
lows, were  shot  morning  and  evening  at  as  nearly  the  desired 
time  as  possible,  and  the  parts  to  be  studied  were  excised  on 
the  spot.  The  pigeons  were  decapitated,  no  anaesthetic  being 
used.  A  pair  of  spinal  ganglia  in  each  case  were  preserved  in 
osmic  acid,  one  per  cent  solution  being  used  as  formerly.  The 
time  was  shortened  to  two  hours'  immersion  on  account  of  the 
small  size  of  the  ganglia.  The  other  parts  were  preserved  in 
saturated  corrosive  sublimate  solution  at  40°  C.  for  four  hours. 

Both  male  and  female  birds  were  employed,  but,  with  one 
exception,  males  were  compared  with  males  and  females  with 
females. 

Results. 

The  following  table  gives  the  results  of  six  experiments  for 
the  parts  studied.  Sections  were  taken  perpendicular  to  the 
surface  of  the  cerebellar  and  occipital  cortex,  longitudinal  sec- 
tions being  made  of  the  spinal  ganglia. 

The  fact  to  strike  one  first  upon  examination  of  the  speci- 
mens or  the  table  is  the  great  amount  of  change  due  to 
a  day's  fatigue.  This  is  seen  to  exceed  anything  obtained  by 
artificial  stimulation  in  almost  all  cases.  The  highest  per  cent 
shrinkage  of  nuclei,  69.7  per  cent,  is  found,  strangely  enough,  in 
the  occipital  cortex  of  a  female  sparrow  April  22,  after  a  long 

*  One  thing,  however,  has  escaped  my  attention,  viz.  the  hardening,  in  osmic  acid, 
of  the  specimens  to  be  compared  was  not  done  at  constant  temperature.  A  slight 
difference,  hence,  between  morning  and  night  temperatures  may  have  had  some  influ- 
ence upon  the  results.  That  this  difference  has  not  complicated  matters  seriously  is 
shown  from  the  fact  that  other  portions  of  the  same  animal  hardened  in  corrosive 
sublimate  at  40*^  C,  and  hence,  not  amenable  to  temperature  variations,  give  results 
equally  good. 


146 


HODGE. 


[Vol.  VII. 


TABLE  X. 

Series  of  Experiments  to  show  Effects  of  a  Day's  Normal  Activity  in  the 
Cells  of  Different  Parts  of  the  Nervous  System. 

(^Corresponding  parts  in  each  animal  treated  in  the  same  manner  and  compared  with 

each  other.') 


Experiment. 


Time. 


Occipital  Cortex. 


Mean  diam. 
of  nuclei. 


Shrink- 
age. 


PuRKiNjE  Cells, 
Cerebellum. 


Mean  diam. 
of  nuclei. 


Shrink- 
age. 


Spinal  Ganglia. 


Mean  diam. 
of  nuclei. 


Shrink- 
age. 


I. 

(Dec.  — ,  '91.) 
English  Sparrow. 

1,  male 

2,  "   

III. 

(Feb.  17,  '91.) 

"  Rainy  day." 

English  Sparrow. 

3,  female 

4,  male 

IV. 

(Apr.  22,  '91.) 
English  Sparrow. 

5,  female 

6,  «      

II. 

(Dec.  — ,  '91.) 

Pigeon. 

1,  male 

2,  "    

V. 

(Apr.  28,  '91.) 

Pigeon. 

3,  female 

4,  "      

VI. 

Swallow 

(^H.  horreorunt). 

(June  10,  '91.) 

1,  male 

2,  "   


7.00  A.M. 
5.30  P.M. 


7.00  A.M. 
4.30  P.M. 


6.30  A.M. 
6.30  P.M. 


8.30  A.M. 
5.30  P.M. 


5.30  A.M. 
7.30  P.M. 


5.00  A.M. 
8.00  P.M. 


8.09  M 
6.72  M 


6.69  fJ. 
443  M 


10.59  M 
9.19  M 


8.85  At 
6.84  M 


43% 


69.7% 


36% 


55-5  % 


8.06  At 

7-75  M 


8.31  At 
6.85  At 


12.74  At 
10.32  At 


9.12  At 
6.32  At 


8% 


43% 


12.04  At 
9-99  M 


54-3  % 


No  difference  observ- 
able, hence  not 
measured. 


51.7% 


10.69  M 
7-44/* 


15-34  M 
12.82  At 


13-88  At 
11.62  At 


64-5  % 


12.00  At 

9.82  At 


64% 


49-5  % 


33-3  % 


45-2  % 


No.  2.]  CHANGES  IN  NERVE  CELLS.  147 

hard  day  of  nest-building.  An  egg  was  found  in  the  lower  por- 
tion of  the  oviduct.  The  next  highest  percentage,  64  per  cent 
and  64  s  per  cent,  expresses  the  amount  of  fatigue  in  the  spinal 
ganglion  cells  of  the  same  bird  and  in  the  cells  of  Purkinje,  a 
male  swallow,  June  10.  Barnyard  pigeons,  fed  a  little  grain  twice 
a  day,  show  considerably  less  fatigue  than  the  wild  birds. 

As  far  as  my  work  would  permit,  some  account  of  the  activity 
of  the  birds  was  kept  during  the  day  of  an  experiment ;  and  a 
day  suited  to  the  purpose  of  the  experiment  was  chosen. 

Experiment  I  was  made  early  in  December,  toward  the  end 
of  a  cold  blustering  snowstorm.     Sparrows  keep  under  pretty 
close  cover  while  such  a  storm  continues,  and  at  its  close  may 
be  seen  out  in  force  and  actively  in  search  of  food.     Advantage 
was  taken  of  a  case  of  this  kind ;  and  the  difference  between 
the  cells  of  the  spinal  ganglia,  the  only  part  taken,  morning 
(Fig.  6)  and  evening  (Fig.  7),  is  readily  seen  by  comparison. 
Although  not  showing  the  highest  shrinkage  per  cent,  the  cells 
of  sparrow  2  (Fig.  7)  do  present  a  somewhat  more  striking  state 
of  dilapidation  than  those  of  sparrow  6,  and  hence  were  chosen 
for  the  plate.     I  suspect  also  that  an  individual  complication  is 
present  here,  in  the  way  of  incipient  starvation,  as  the  crop  of 
this  sparrow  was  empty,  and  there  was  little  food  in  the  gizzard, 
and  this  at  night  when  both  are  usually  well  filled.     The  proto- 
plasm is  seen  to  be  extremely  vacuolated  and  the  nuclei  much 
shrunken.     The  peculiar  clear  spaces  which  form  such  a  marked 
feature  in  the  cells  of  sparrow   i   (Fig.  6)  are  somewhat  aside 
from  the  line  of  our  thought  at  present,  and  will  be  discussed 
on  a  later  page. 

Experiment  II  was  made  about  the  same  time,  and  is  simply 
confirmatory  of  Experiment  I.  Shrinkage  of  the  nuclei  in  the 
pigeon  is  nearly  as  marked  as  in  the  sparrow.  Vacuolation  of 
protoplasm  is  not  so  striking,  although  present. 

Experiment  III  deserves  special  remark.  It  was  made  with 
the  single  purpose  of  confirming  Experiments  I  and  II.  But 
on  the  morning  of  February  17,  shortly  after  sparrow  3  had 
been  shot,  it  began  to  rain,  and  continued  nearly  the  whole  day, 
a  steady,  warm,  foggy  spring  rain.  In  the  dense  cover  of  the 
pine  trees  over  my  window  the  sparrows  spent  the  day  scolding 
and  chattering  at  a  great  rate.  None  were  observed  flying 
about.     At  first  I  decided  to  abandon  the  experiment,  thinking 


148  HODGE.  [Vol.  VII. 

that  I  would  find  little  evidence  of  fatigue  on  such  a  day.  On 
second  thought,  however,  I  concluded  to  make  a  "rainy  day" 
experiment  of  it  and  see  what  might  be  the  result,  I  little 
expected  the  sharp  and  somewhat  amusing  result  expressed  in 
the  table.  Not  an  observable  sign  of  fatigue  was  to  be  seen 
in  the  spinal  ganglia ;  while  traces  of  fatigue  were  slight  in  the 
cells  of  Purkinje.  Perfectly  clear,  however,  were  the  marks  of 
fatigue  in  the  nuclei  of  the  occipital  cortex,  as  though,  while 
confined  by  the  rain,  the  little  birds  had  kept  up  a  deal  of  think- 
ing. The  experiment  is  further  complicated  by  the  fact  that 
upon  the  night  of  February  14,  in  accordance  with  the  time- 
honored  custom  of  St.  Valentine's  day,  the  boys  had  "shelled" 
the  windows  of  Worcester  with  peas.  The  subsequent  thaw 
had  left  them  soft  and  swollen  upon  the  surface  of  the  snow ; 
and  as  a  result  the  crops  and  gizzards  of  the  sparrows  on  Feb- 
ruary 17  were  filled  with  peas  both  morning  and  night.  Indeed, 
it  would  require  but  trifling  effort  on  such  a  day  of  plenty  for  a 
sparrow  to  lay  in  a  supply  of  food  sufficient  for  several  stormy 
days. 

In  order  to  have  represented  in  the  plates  as  many  experi- 
ments upon  as  many  of  the  different  animals  as  possible.  Figs. 
8  and  9  were  taken  from  the  occipital  cortex  of  Figs.  3  and  4. 
These  figures  show  fairly  well  the  difference  between  the 
morning  and  evening  cells  of  the  other  birds. 

It  will  be  specially  noted  (Figs.  8  and  9,  and  12  and  13)  that 
whereas,  in  spinal  ganglion  cells  with  capsules,  loss  of  sub- 
stance in  the  protoplasm  is  shown  by  vacuolation  with  little 
shrinkage  of  cell,  in  the  cerebrum  and  cerebellum  the  cells 
shrink  bodily.  This  is  expressed  in  part  at  least  by  enlarged 
pericellular  lymph  spaces. 

Experiment  IV  was  purposely  made  upon  a  warm,  bright  day, 
April  22,  when  the  sparrows  were  most  busily  at  work  nest- 
building,  with  purpose  also  upon  female  sparrows. 

"  Fur  den  Spatz  ist  das  Plaisir, 
Fur  die  Spatzin  sind  die  Pflichten !  " 

Effects  of  the  day's  work  are  seen  from  the  table  to  be  quite 
evenly  distributed  over  the  parts  of  the  nervous  system  exam- 
ined. This  is  true  for  all  cases  except  for  No.  Ill,  the  rainy 
day  experiment 


No.  2.]  CHANGES  IN  NERVE  CELLS, 


149 


Experiment  V  was  made  for  purposes  of  confirmation  simply, 
and  calls  for  no  special  mention. 

Perhaps  the  most  active  bird  that  we  have  is  the  swallow. 
Its  food  consists  of  insects  taken  entirely  on  the  wing.  Quick, 
vigorous,  purposeful,  careful  in  all  its  actions,  it  must  require  an 
enormous  amount  of  nervous  energy  to  co-ordinate  its  countless 
movements  for  a  long  summer's  day.  All  day  long,  whenever  I 
chance  to  look  up  from  my  work,  I  see  this  bird  flitting  and 
sailing  and  circling,  fluttering  up  and  swooping  down.  There 
is  nothing  lazy  or  stupid  about  the  swallows.  When  their 
work  is  done,  they  play  games  and  fly  races  ;  and  with  all  the 
energy  required  for  flying,  they  have  enough  left  to  do  no  end 
of  talking;  for  their  cheerful  "zwitschern"  is  continually  in 
my  ears  while  I  write.  At  one  hundred  miles  an  hour,  for  ten 
hours,  —  and  I  have  observed  them  as  early  as  five  o'clock  in 
the  morning,  and  as  late  as  eight  at  night, — a  swallow  might 
cover  a  distance  of  one  thousand  miles  in  a  single  day,  and  day 
after  day.  If  a  bullet  of  the  same  weight  were  to  traverse  the 
same  distance  at  the  same  speed,  an  enormous  explosion  of 
energy  would  be  required,  and  the  living  arrow  can  require  no 
less. 

Accordingly,  for  Experiment  VI,  swallows  were  employed.^ 
A  day  was  chosen,  when  weather  predictions  were  favorable,  at 
a  time  (June  10)  when  swallows  are  busiest  feeding  their  young. 
I  reached  Goes'  Pond  in  the  morning,  before  a  swallow  was  in 
sight.  At  just  five  o'clock,  a  large  male  swallow  flitted  from 
the  eaves  of  an  ice-house,  and,  alighting  on  a  telephone  wire, 
began  preening  his  feathers  for  his  morning  flight.  Within  five 
minutes,  his  brain  and  spinal  ganglia  were  in  their  proper 
hardening  fluids,  osmic  acid  and  mercuric  chloride. 

Again,  at  a  little  before  seven,  I  took  my  stand  by  the  same 
pond.  Swallows  were  circling  thick.  I  waited  until  a  few 
minutes  before  eight,  when  all  but  two,  both  males,  had  gone 
home  for  the  night.  One  of  those  flitted  too  close  to  my  gun, 
and  came  down  with  a  broken  wing ;  and  by  eight  o'clock  his 
brain  and  ganglia  were  treated  like  those  of  his  brother  of 
the  morning.     I  could  not,  however,  help  making  the  note,  as 

1  The  writer  takes  pleasure  in  acknowledging  the  courtesy  of  Messrs.  E.  A.  Brackett 
and  Edward  H.  Lathrop,  Commissioners  of  Fish  and  Game  for  the  State  of  Massa- 
chusetts, in  granting  the  official  permit  under  which  these  birds  were  killed. 


I^o  HODGE.  [Vol.  VII. 

I  watched  them  flying  at  evening,  "  They  don't  seem  tired 
one  bit." 

From  results  of  experiments  upon  birds,  with  the  great 
amount  of  matter  lost  from  the  nervous  system  during  a  day's 
work,  I  feel  confident  in  chancing  the  prediction  that  a  small, 
active  bird,  an  English  sparrow,  for  example,  could  not  be  kept 
awake  and  fluttering  a  single  night  without  fatal  results.  I  had 
hoped,  instead  of  the  prediction,  to  have  been  able  to  report  an 
experiment  of  this  sort ;  but  time  and  the  opportunity  have  not 
been  conjoined  thus  far. 

In  addition  to  signs  of  fatigue  present  everywhere  in  the 
parts  examined,  the  brains  of  these  swallows  held  in  waiting  an 
agreeable  surprise.  By  reference  to  the  table  (X,  Exp.  VI),  it 
will  be  noticed  that  the  cerebellum  shows  the  highest  per  cent 
of  loss,  nearly  ten  per  cent  more  than  the  occipital  cortex.  The 
same  thing  is  true  of  the  pigeon,  but  not  of  the  sparrows. 
Extreme  cases  naturally  make  a  much  stronger  impression  than 
mean  cases  of  nearly  the  same  magnitude  ;  and  such  an  extreme 
case  has  been  shown  in  Fig.  12  (PI.  VIII),  taken  from  the 
cerebellum  of  the  night  swallow.  It  is  to  be  compared  with 
Fig.  13,  drawn  from  the  morning  bird.  Cells  could  easily  have 
been  selected  for  measurement  which  would  have  shown  a  much 
greater  percentage  of  loss;  but,  this  not  being  allowable,  the 
figures  in  the  table  give  presumably  a  fair  average,  while  Figs. 
12  and  13  present  the  extremes.  From  the  figures,  too,  the 
nuclei  of  Deiter's  cells  are  seen  to  have  shrunken,  as  well  as 
those  of  Purkinje.  To  the  cerebellum  is  generally  ascribed  the 
work  of  muscular  co-ordination,  and  where  could  be  sought  an 
instance  of  more  delicate  manipulation  of  muscles  than  must  be 
required  to  drive  the  wing  of  a  swallow  as  it  flits  and  whirls  and 
balances  and  wheels  and  darts,  the  whole  day  long  }  In  the 
pigeon  and  sparrows,  although  the  nuclei  of  the  Purkinje  cells 
show  great  shrinkage,  these  extreme  cases  are  not  met  with. 
These  birds  use  their  legs  as  well  as  wings. 

To  discuss  a  result  of  this  kind,  however,  carries  us  far  ahead 
of  our  present  purpose  and  knowledge.  It  is  exactly  what 
might  have  been  expected,  had  the  idea  occurred;  yet,  now 
that  it  stands  before  us,  we  are  afraid  to  believe  it ;  and  will 
promise  not  to,  until  further  experiment  is  made.  But  the  time 
may  come  when  we  shall  be  able  to  study  some  phases  of  local- 


No.  2.]  CHANGES  IN  NERVE  CELLS.  151 

ization  in  the  brain  by  means  of  changes  in  the  cells  due  to 
fatigue. 

The  pigeons  were  not  introduced  solely  to  add  variety  to  the 
list  of  animals  used ;  but  with  a  distinct  purpose  of  another 
kind.  Arrangements  had  been  made  with  a  pigeon  fancier  ^  of 
Worcester,  to  furnish  a  number  of  trained  homing  pigeons. 
These  birds,  if  taken  away  from  their  loft  and  liberated,  are 
said  to  fly  without  alighting  during  the  first  day,  or  until  the 
loft  is  regained.  Records  have  been  scored  of  over  five  hundred 
miles,  air-line  distance,  on  the  day  of  liberation  {jy,  p.  366), 
the  birds  coming  to  loft,  I  am  told,  too  fatigued  to  hold  up  their 
wings  from  the  floor.  It  was  intended  to  make  at  least  one 
experiment  with  them  to  show  extreme  fatigue,  fatigue  from 
which,  I  am  informed,  pigeons  require  not  only  a  night's  sleep, 
but  several  days'  time,  to  fully  recover.  The  birds  were  lost  in 
course  of  training,  and  I  was  obliged  to  leave  Worcester  before 
others  could  be  obtained.^  I  had  intended  using  the  common 
pigeons  as  normals,  to  show  the  effect  of  a  moderate  day's  work, 
for  the  homing  pigeons,  which,  it  was  hoped,  would  demonstrate, 
by  comparison,  extreme  fatigue. 

Failing  of  the  homing  pigeons  was  possibly,  for  the  present 
a  piece  of  good  fortune,  for  I  bethought  myself  of  another  ani- 
mal, the  proverbially  "busy  bee."  From  these,  at  any  rate,  I 
have  obtained  most  striking  results.  They  may  be  seen  at  a 
glance  by  comparing  Fig.  10  (evening)  with  Fig.  1 1  (morn- 
ing). 

On  the  morning  of  June  10,  after  securing  my  swallow,  I 
stationed  myself  by  a  patch  of  raspberry  bushes  in  full  bloom 
and  within  a  stone's  throw  of  a  small  apiary,  and  watched  for 
the  bees  to  come.     At  six  o'clock  sharp  they  came.     The  first 

^  The  writer  refers  to  Mr.  Frank  Keith,  to  whom  he  is  under  great  obligations  fur 
kind  assistance  and  valuable  information  regarding  the  use  of  homing  pigeons. 

*  Homing  pigeons  are  expensive,  when  well  bred,  costing,  minimum  price,  six 
dollars  per  pair,  for  young  birds.  Their  training  may  cost  an  indefinite  amount 
more.  I  have,  however,  to  thank  Dr.  S.  Weir  Mitchell  for  a  fine  loft  of  about 
thirty  blooded  homing  pigeons;  a  number  of  which  are  being  trained  at  this 
writing  for  longest  possible  flights  in  order  to  furnish  material  for  the  above- 
mentioned  experiments.  It  is,  however,  a  much  longer  undertaking  than  I  antici- 
pated. The  birds  attain  full  maturity  in  not  less  than  four  years.  Young  pigeons 
lack  the  mental  development,  the  grit,  and  perseverance,  to  put  forth  the  great  amount 
of  effort  desired.     But  the  experiments  will  be  reported  in  due  time. 


JC2  HODGE.  [Vol.  VII. 

six  bees  I  could  catch  were  quickly  decapitated,  the  brains  re- 
moved, and  three  were  dropped  into  one-half  per  cent  osmic 
acid,  and  three  into  saturated  mercuric  chloride  solution. 

While  watching  the  swallows  the  same  evening,  I  caught  six 
bees  at  about  seven  o'clock.  These  were  laid  aside  in  a  net,  and 
with  a  second  net  I  caught  six  more.  I  then  released  the  first 
six  and  repeated  the  operation  ;  until,  at  about  half-past  seven, 
when  no  more  bees  could  be  found  on  the  flowers,  I  retained 
the  six  bees  last  captured.  Before  taking  their  brains,  I  watched 
them  for  the  space  of  perhaps  ten  minutes.  Five  sat  perfectly 
still  in  the  net ;  one  buzzed  angrily  and  without  cessation  the 
whole  time,  in  fact  until  his  head  came  under  the  scissors. 
This  one  was  named  "lively  bee,"  and  his  brain  was  kept  sepa- 
rate from  the  rest.  The  brains  were  treated,  of  course,  Hke 
those  of  the  morning  lot. 

The  preparation  continued  until  eighty  per  cent  alcohol  was 
reached,  when  the  morning  brains  were  allowed  to  remain  enough 
longer  to  catch  up ;  and  then  all  were  arranged  in  pairs  upon 
slips  of  cardboard,  as  described  on  page  115.  With  the  excep- 
tion of  No.  12  ("lively  bee"),  they  were  paired  indiscriminately, 
osmic  acid  brains,  morning,  with  osmic  acid  brains,  evening ; 
the  mercuric  chloride  specimens  in  the  same  way ;  and  for  con- 
venience they  were  numbered,  the  odd  numbers  representing 
morning,  the  even  numbers  evening  bees. 

The  attempt  was  made  to  measure  the  nuclei  after  the  manner 
of  foregoing  experiments  ;  and  although  one  may  see  from  Figs. 
10  and  1 1  how  far  from  satisfactory  such  a  method  might  be, 
still  the  results  will  be  given  in  tabulated  form. 


X 


No.  2.] 


CHANGES  IN  NERVE  CELLS. 


153 


TABLE   XL 
Honey-Bee  Experiments. 

Antennal  Lobe. 


Number  Mean  diameter 

of  bee.  of  nuclei. 

I 4-53  M 

2 3.25  " 


Diff. 


1.28  " 


Diff. 


3 409  " 

4 2.94  " 

115" 

4.65" 

3-25  " 

1 .40  " 


Diff. 


f      7- 


Diff. 


I       9- 
\     10. 


Diff. 


4.60  " 

390  " 
.70" 

4-56  " 

3-96  " 

.60" 

4.46  " 


12  ("  Lively  bee  ") 4-35  " 

Diff II" 

Minimal 

(barring  No.  n). 

3 4-09/* 

10 3-96  " 

Diff 13  " 

Maximal. 

5 465  II 

4 2.94  " 

Diff 1.71  " 


Per  cent 
of  shrinkage. 

64% 


73% 
73% 
34% 
33% 
8% 

9% 
75% 


Arranged,  as  they  were,  at  random,  we  have  the  right  to  pair 
any  morning  bee  with  any  evening  bee.  This  gives  us  as  a 
minimal  shrinkage  nine  per  cent,  as  a  maximal  seventy-five  per 
cent.  Although  I  do  not  attach  exact  values  to  these  figures, 
they  express  a  truth  easily  observed  in  the  specimens ;  viz. 
the  wide  difference  between  them.  The  fact  is  brought  out  by 
comparing  morning  bees  with  morning  bee.s,  and  evening  bees 
with  evening  bees.  Here  we  observe  that  the  morning  diam- 
eters, 4.09,  4.53,  4.46,  4.56,  4.60,  4.65,  are  somewhat  more  uni- 
form than  the  evening  diameters,  2.94,  3.25,  3.25,  3.90,  3.96  (4.35) ; 
the  greatest  difference  between  morning  diameters  being  .56  (m, 


1^4  HODGE.  [Vol.  VII. 

between  the  evening  diameters  1.02  11,  barring  No.  12  (with  No. 
12  1. 41  /i) ;  while  the  greatest  difference  between  morning  and 
evening  diameters  is  1.7 1  /u,. 

Did  I  feel  that  the  above  figures  were  more  trustworthy,  I 
would  go  into  their  manipulation  more  in  detail.  Enough  has 
been  given  to  make  plain  the  following  points.  First,  the  nerve 
cells  of  a  number  of  bees'  brains  are  in  a  more  uniform  condi- 
tion in  the  morning  than  in  the  evening.  Second,  they  differ 
in  appearance,  or  condition,  from  one  another  somewhat  in  the 
morning  and  a  great  deal  in  the  evening.  Working  bees  from 
the  same  hive  would  strike  one  as  being  as  much  alike  as  it 
would  be  possible  to  conceive  of  a  number  of  animals.  Whence 
then  are  these  differences } 

No  individual  difference  of  size  was  noticed.  All  honey-bees 
which  are  out  gathering  honey  from  the  flowers  must  have  an 
abundance  of  food  on  hand;  and  the  food  of  bees  in  a  given 
place  and  time  must  be  the  same.  Hence  no  differences  in 
nutrition  would  be  likely  to  occur. 

If  six  bees  were  exactly  alike  in  the  morning,  their  brain  cells, 
of  course,  should  appear  alike,  if  examined  by  the  same  method. 
If  all  the  six  should  fly  exactly  the  same  distance  in  the  same 
time,  i.e.  do  exactly  the  same  amount  of  work,  we  should  expect 
to  find  their  brains  in  the  same  condition  again  at  night. 

There  are  two  important  variables  present  which  unfortu- 
nately we  know  little  about.  7/" the  bees  are  alike;  if  the  work 
is  alike.  The  work  may  vary  ;  the  bees  may  vary  within  indefi- 
nite limits. 

With  reference  to  the  amount  of  work  done  by  a  bee,  we 
know  almost  nothing.  Lubbock  (46,  p.  276)  and  the  Peck- 
hams  (65)  have  counted  the  number  of  trips  a  bee  or  wasp 
may  make  in  a  day,  and  this  number  varies  ;  but  who  has  ever 
followed  a  bee  in  one  of  its  flights  t  Whether  a  load  of  honey 
be  found  near  or  far  away  must  cause  the  flights  to  vary.  Still, 
it  is  evident,  these  two  variables,  length  and  number  of  flights, 
may  be  so  combined  as  to  produce  a  constant  amount  of  work. 

When  a  boy  in  college,  the  writer  owned  some  bees.  Every 
morning,  in  the  busy  season,  a  few  bees  could  be  found  dragged 
out  of  the  hive  dead.  Every  evening  might  be  seen  in  the 
grass  near  a  hive,  bees  with  the  frayed  wings  and  abraded  hairs 
betokening  old  age,  heavily  laden,  but  too  tired  to  lift  them- 


No.  2. J  CHANGES  IN  NERVE   CELLS.  155 

selves  in  the  air  for  the  short  space  necessary  to  regain  the  hive. 
With  food  and  parentage  and  every  element  of  living  so  exactly 
alike,  observations  like  the  above  have  led  me  to  think  that  the 
only  difference  between  the  bees  in  a  hive,  a  difference  which 
might  bring  about  a  complication  of  results  like  that  occurring 
in  Table  XI,  must  be  a  difference  of  age.  This  would  naturally 
lead  to  a  difference  of  work. 

Figs.  II  and  10  (PI.  VIII)  are  drawn  respectively  from 
bees  3  and  4.  Although  paired  together  by  accident,  they 
serve  to  illustrate  my  point  better  than  any  of  the  others.  In 
No.  3,  Fig.  II,  we  notice  that  in  cells  of  about  the  same  size 
the  size  of  the  nuclei  varies  considerably,  and  a  good  many 
appear  shrunken  and  somewhat  angular  in  outline.  In  all  the 
other  morning  bees  they  are  more  uniform.  Is  it  not  possible 
that  this  is  the  case  of  an  old  bee,  in  which  the  balance 
between  repair  and  waste  has  turned  toward  the  side  of  waste  } 
The  night's  rest  is  no  longer  sufficient  for  complete  recovery 
from  loss  due  to  the  day's  work.  Bee  No.  4  (Fig.  10)  is  the 
extreme  case  in  the  series.  In  no  other  one  are  the  nuclei 
quite  so  shrunken  and  the  cell  protoplasm  so  extremely  vacuo- 
lated. I  cannot  do  less  than  make  the  remark  regarding  this 
bee,  that  possibly  it  might  have  fallen  by  the  hive  to  die  that 
night. 

Bee  No.  12  is  an  evening  bee  that  shows,  so  far  as  brain  cells 
or  actions  go,  no  signs  of  fatigue.  If  I  were  given  a  section 
of  any  of  the  other  bees'  brains  and  asked :  "  Morning  or 
night } "  I  could  tell  which.  With  this  one  I  should  say, 
"Morning."  In  strictest  logic,  therefore,  I  am  obliged  to  say, 
that  in  five  cases  out  of  six  the  cells  of  bees'  brains  show, 
at  night,  effects  of  the  day's  fatigue.  In  one  case  in  six 
this  does  not  appear.  My  own  supposition,  however,  is  that 
No.  1 2  is  a  young  bee,  out  for  a  stroll  in  the  cool  of  the  even- 
ing.i 

The  antennal  lobes  were  chosen  for  special  study,  because 
the  cells  were  uniform  in  size,  shape,  and  grouping,  and  were 
easily  located  so  that  certainty  of  comparing  similar  parts  was 
attained.     Other   regions   presented   similar   appearances,    but 

'  The  writer's  regret  for  neglecting  to  observe  "  age  signs "  in  the  above  bees 
can  better  be  imagined  than  expressed.  However,  experiments  are  under  way  to 
remedy  this  defect. 


J  ^5  HODGE.  [Vol.  VII. 

were  less  regular  and  well  defined.  The  lobes  were  located 
by  the  aid  of  Riley's  (71)  description  of  the  locust's  brain. 

Besides  those  tabulated,  several  preliminary  experiments  were 
made,  two  upon  bumble-bees  and  two  upon  honey-bees.  As 
these  all  show  evening  fatigue,  the  ratio  of  fatigue  cases  is 
much  increased. 

This  closes  the  list  of  diurnal  fatigue  experiments.  The 
writer  regrets  the  absence  of  a  mammal  from  the  series.  One 
experiment  upon  a  dog  was  attempted,  but  terminated  unfortu- 
nately.^ I  hope,  however,  in  the  near  future  to  be  able  to  make 
some  experiments  upon  mammals  which  shall  supply  this  de- 
ficiency. At  present  I  have  the  following  observations  to 
append. 

The  "  Worcester  Fur  Company  "  is  an  organization  of  gentle- 
men upon  the  principle  that  foxes  should  be  chased  at  least  one 
day  in  the  year.  At  their  meet  the  Company  placed  two  of 
the  carcasses  at  Dr.  Donaldson's  disposal.  The  brains  were 
used  for  comparative  anatomy  specimens.  I  obtained  spinal 
ganglia  of  each,  which,  compared  with  those  of  a  dog  of  about 
the  same  size,  show  nearly  as  much  difference  as  is  seen  be- 
tween Figs.  I  and  2.  No  data  were  obtained  as  to  how  long  the 
foxes  had  been  chased.  The  method  of  hunting  in  that  section 
being  to  shoot  the  fox  at  sight,  no  estimate  of  this  quantity  can 
be  made.  They  may  have  been  shot  as  they  jumped  from  cover 
or  after  the  hounds  had  chased  them  for  several  hours.  Signs 
of  great  fatigue,  compared  with  what  has  been  found  in  birds 
and  bees,  are  certainly  not  present. 

Without  exception  the  motor  cells  in  the  ventral  horns  of 
human  spinal  cords  that  have  come  under  my  observation 
present  considerably  shrunken  nuclei.  In  the  spinal  cord  of  a 
hydrophobia  patient,^  however,  this  phenomenon  is  presented 
in  an  extreme  degree.  Characteristic  ecchymoses  in  the  gray 
matter  were  numerous  (17,  Vol.  II,  p.  847).  According  to 
Cowers,  changes  in  ganglion  cells  in  hydrophobia  are  trivial. 
Popow    (^6)    in   a   single   case   notes   little   of   interest   to   us 

1  After  working  the  dog  from  five  o'clock  in  the  morning  until  three  in  the  after- 
noon, racing  him  through  woods  and  swimming  him  in  ice-water,  which  he  did 
willingly,  the  dog  bolted  and  was  not  seen  again  for  three  months. 

2  For  the  above  material  I  am  indebted  to  the  courtesy  of  Dr.  R.  H.  Chittenden 
of  New  Haven,  Conn. 


No.  2.]  CHANGES  IN  NERVE  CELLS.  157 

except  pigmentary  degeneration  ;  and  this  may  occur  in  almost 
any  specimen.  No  special  amount  of  pigment  was  remarked 
in  the  case  in  hand.  Measuring  a  set  (in  this  case  20)  of 
nuclei  in  a  so-called  normal  cord  for  comparison  gave  the  fol- 
lowing result  :  — 

Nuclei  of  normal  cord ;  mean  diameter  .         .         .     4.30 /u, 

Nuclei  of  hydrophobia  cord  ;  mean  diameter  .         .     3.12 /a 

Volume  per  cent  smaller      .         .         .         .         •        59  % 

I  throw  out  the  above  merely  as  a  straw  which  may  serve  to 
show  the  direction  of  the  current.  We  may  have  further  use 
for  the  material  at  some  future  time. 

I  cannot  close  without  mentioning  by  way  of  preliminary 
communication  the  peculiar  appearances  found  quite  constantly 
in  osmic  acid  preparations  of  the  ganglion  cells  of  birds.  They 
are  represented  in  Fig.  6,  drawn  throughout  by  the  aid  of  a 
camera  lucida.  A  few  are  seen  in  Fig.  7 ;  viz.  the  vacuoles  with 
sharp  outlines  and  definite  shape.  The  majority  of  the  vacuoles 
in  Fig.  7  are  easily  seen  to  differ  in  these  respects  from  those 
in  Fig.  6.  In  corrosive  sublimate  preparations  they  are  seen 
to  be  present,  but  are  masked  by  granules. 

When  first  noticed,  their  definite  form  was  thought  to  indi- 
cate bodies  of  a  crystalline  nature  in  the  protoplasm  of  the  cells. 
They  were  accordingly  tested  with  polarized  light,  but  were 
found  to  be  inert. 

Altmann  (2)  states  that,  whereas  fats  on  treatment  with 
osmic  acid  become  insoluble  in  alcohol,  certain  fatty  acids 
remain  soluble.  Therefore  tissues  hardened  in  osmic  acid,  if 
they  contain  droplets  or  crystals  of  fatty  acid  after  dehydration 
in  alcohol,  present  vacuoles  holding  the  shape  of  the  fatty  acid 
particles.  It  was  thought  that  this  might  account  for  the  lack 
of  any  action  upon  polarized  light.  Accordingly  a  fresh  morn- 
ing sparrow  was  taken  and  the  ganglion  cells  crushed  out 
quickly  and  examined  under  polarized  light.  The  result  was 
doubtful.  If  any  crystalline  bodies  were  present,  they  vanished 
almost  instantaneously.  In  the  liver,  among  fat  droplets,  which 
shone  brightly  on  the  dark  field,  were  a  few  shining  particles 
shaped  like  those  in  the  ganglion  cells,  but  these  were  quite 
permanent.  The  same  forms  are  found  in  the  osmic  acid  liver. 
In  the  oil  gland,  freshly  crushed  out,  among  sheaves  of  fatty 


158  HODGE.  [Vol.  VII. 

acid  crystals,  particles  of  the  above  form  were  quite  numerous, 
but  these  also  had  no  tendency  to  vanish. 

Grandis  (16)  has  obtained  staining  of  intranuclear  crystals 
by  long  immersion  in  osmic  acid.  This  was  also  tried,  teasing 
out  the  ganglion  cells  in  osmic  acid,  but  with  uncertain  or  nega- 
tive results.  Miss  Leonard  (41,  p.  39)  also  calls  attention  to 
crystals  or  crystal-like  bodies  in  the  liver  cells  of  frogs. 

Appearances  of  this  form  have  a  somewhat  wide  distribution 
in  avian  tissues,  so  far  as  examined.  I  have  found  them  in  the 
spinal  and  sympathetic  ganglia  of  all  birds  studied,  in  the  livers 
of  several,  all  which  were  examined  for  them,  in  the  uropygial 
gland  of  two  (only  ones  examined),  and  in  the  secreting  cells 
of  the  oviducts  of  two  fowls.  They  are  most  numerous  in  the 
ganglion  cells  and  oil  gland,  and  occur  somewhat  sparsely  in 
the  other  locations.  Absolute  identity  in  these  different  cases 
is,  of  course,  not  established,  farther  than  such  identity  is  indi- 
cated by  similarity  between  the  forms  observed. 

In  general,  as  indicated  in  the  figures  (6  and  7,  PI.  VIII), 
these  figures  are  numerous  in  morning  cells  and  fewer  in  those 
of  the  evening,  their  place  being  represented  by  more  or  less 
irregularly  shaped  vacuoles.  It  is  as  impossible  to  stain  them 
as  it  is  to  stain  the  vacuoles  of  the  evening  cells.  In  fact,  as 
they  exist  in  the  sections,  I  suppose  they  must  be  considered 
vacuoles ;  their  uniform  and  definite  shape,  however,  indicates 
that  they  are  produced  by  solution  of  some  formed  substance  in 
the  cells.  That  they  cannot  be  artifacts  is  proved  by  their  form 
and  arrangement  in  the  cells,  by  their  difference  in  size  in  differ- 
ent cells,  by  their  greater  numbers  in  morning  material,  and  by 
their  entire  absence  from  frog  and  mammalian  tissues,  treated 
by  the  same  methods. 

I  will  not  attempt  to  describe  these  appearances  more  in  detail 
as  to  shape,  size,  and  origin  until  further  experiments  are  made. 

Conclusions. 

Metabolic  changes  in  nerve  cells  are  certainly  as  easy  to 
demonstrate,  microscopically,  as  similar  processes  in  gland  cells. 
They  may  be  demonstrated  equally  well,  and  are  the  same  in 
character,  either  by  artificial  or  natural  methods. 

The  principal  changes  thus  far  observed  are  :  for  spinal  gan- 


No.  2.]  CHANGES  IN  NERVE  CELLS.  159 

glion  cells  of  frog,  cat,  dog,  under  electrical  stimulation  ;  for  spinal 
glanglion  and  brain  cells  of  English  sparrow,  pigeon,  swallow, 
a.n.d  for  drain  cells  of  honey-bee,  tinder  normal  fatigue :  — 

A.  For  nucleus:  i.  Marked  decrease  in  size.  2.  Change 
from  smooth  and  rounded  to  a  jagged,  irregular  outline.  3.  Loss 
of  open  reticulate  appearance  with  darker  stain. 

B.  For  cell-protoplasm:  i.  Slight  shrinkage  in  size,  with 
vacuolation  for  spinal  ganglia ;  considerable  shrinkage,  with 
enlargement  of  pericellular  lymph  space  for  cells  of  cerebrum  and 
cerebellum.    2.  Lessened  power  to  stain  or  to  reduce  osmic  acid, 

C.  For  cell  capsule,  when  present :  Decrease  in  size  of  nuclei. 

D.  Individual  nerve  cells,  after  electrical  stimulation,  recover, 
if  allowed  to  rest  for  a  sufficient  time.  The  process  of  recovery 
is  slow,  from  five  hours'  stimulation,  being  scarcely  complete 
after  twenty-four  hours'  rest. 

E.  Provisional  curves  have  been  constructed  from  direct 
observations  of  the  nerve  cell  to  represent  the  processes  of 
fatigue  and  recovery.  These  curves  indicate  that  the  nerve  cell 
tires  or  rests  rapidly  at  first,  then  slowly,  then  more  rapidly 
again.  That  is,  the  curve  of  nerve-cell  rest  or  fatigue  is  not  a 
straight  line. 

I  part  with  this  manuscript  with  the  feeling  that  I  have  not 
done  justice  either  to  my  material  or  to  the  subject.  Interrup- 
tion has  been  unavoidable,  and  stress  of  other  work  great.  It 
is,  at  best,  but  a  small  beginning  in  a  field  the  bounds  of  which 
have  opened  out  much  faster  than  I  have  been  able  to  advance. 
With  greater  opportunity  and  facilities  for  work  which  Clark 
University  will  afford,  it  is  to  be  hoped  that  something  may 
be  accomplished  during  the  coming  year. 

In  order  to  properly  define  results  already  obtained,  it  will 
be  necessary  to  know  two  things.  First,  exactly  what  changes 
take  place  in  nerve  cells  under  variations  of  food  and  water 
supply.  Second,  what  changes,  if  any,  take  place  in  nerve 
cells  from  birth  to  death  from  old  age,  from  "rejuvenation"  to 
"senescence."  ^ 

U.NivERsiTY  OF  "Wisconsin,  Madison,  Wis. 
Aug.  27,  1892. 

'  An  abstract  of  the  above  paper  with  demonstration  of  specimens  was  given 
before  the  American  Physiological  Society  at  the  Congress  of  American  Physicians 
and  Surgeons,  Washington,  D.C,  September  22,  1891. 


l6o  HODGE.  [Vol.  VII. 


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1 66  HODGE. 


EXPLANATION   OF   PLATE  VIL 

Electrical  Stimulation.  —  Cats. 

Fig.  I.  Normal.    Cat  17.     Left  spinal  ganglion  of  ist  thoracic  pair.    Osmic  acid. 

Fig.  2.    Stimulated ^  hrs.     Cat  17.     Mate  ganglion  to  Fig.  i.     Osmic  acid. 

By  comparing  Fig.  2  with  Fig.  i  is  seen  the  effect  of  severe  work  (15  seconds' 
stimulation  to  45  seconds'  rest)  for  5  hours,  the  nuclei  becoming  darker,  shrunken 
and  irregular  in  outline,  protoplasm  somewhat  vacuolated. 

Fig.  3,  Normal.  Cat  17.  Three  cells  from  left  ganglion  of  8th  thoracic  pair. 
Corrosive  sublimate,  40°;  4  hrs.     Gaule's  quadruple  stain. 

Fig.  4.  Stimulated ^  hrs.  Cat  1 7.  Five  cells  from  mate  ganglion  to  Fig.  3.  Like 
treatment. 

Compare  Figs.  3  and  4  for  effect  of  stimulation  upon  size  and  character  of  nucleus. 

Fig.  5.  Rested  6\  hrs.  Cat  16.  Four  cells  from  right  8th  cervical  ganglion, 
stimulated  5  hrs,  rested  b\  hrs.  The  normal  of  Fig.  5  is  like  Fig.  3.  Preparation 
same  as  for  3  and  4. 

Compare  Figs.  5  and  4  for  influence  of  rest. 

The  above,  Figs.  1-5,  were  drawn  under  magnification  of  Zeiss  apochromatic, 
oc.  4,  obj.  2  mm.,  oil  immersion  (=x  500  diameters).  Outlines  drawn  by  aid  of 
Zeiss  camera  lucida,  after  Abbe  (with  longer  arm) .  Cells  of  each  figure  contiguous, 
as  shown  by  connective  tissue,  etc.,  uniting  them. 


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HODGE. 


EXPLANATION   OF   PLATE   VIIL 


Normal  Daily  Fatigue.  —  Birds  and  Bees. 


Fig.  6.  Morning.  Portion  of  field  from  3d  brachial  ganglion  of  English  sparrow, 
killed  December  — ,  '91,  at  7  A.M.     Osmic  acid,  I  %,  2  hrs. 

Fig.  7.  Evening.  Field  from  corresponding  ganglion  of  English  sparrow,  killed 
same  day  (as  Fig.  6),  at  7.30  p.m.     Like  preparation  with  Fig.  6. 

Figs.  6  and  7  demonstrate  extreme  daily  fatigue  with  probably  some  lack  of  food. 
The  queer-shaped  clear  spaces  in  Fig.  6  are  seen  to  be  replaced  to  a  great  degree  in 
Fig.  7  by  faintly  outlined,  irregular  vacuoles.  Nuclei  (Fig.  7)  appear  shrunken,  as 
in  cases  of  electrical  stimulation. 

(Occipital  cortex  of  pigeons.     April  28,   '91 ;    killed  at  5.30 
A.M.    and    7.30   P.M.      Corrosive   sublimate,   40°  C.  4  hrs. 
Sections  3  m  thick.     Gaule's  stain,  on  the  slide. 
Figs.  6,  7,  8,  and  9,  camera  lucida  drawings,  magnification  Zeiss,  oc.  6,  obj.  2  mm., 
oil  immersion  (=  X  750  diameters),  apochromatic  system. 

■  Median  subdivision  antenary  lobe  of  brain  of  honey  bee. 
Taken  June  10,  6  A.M.  and  7.30  P.M. 
Fig.  II.   Morning.       Osmic  acid  \  %,  2  hrs.     Sections  3  y.  thick,  stained  in  slide 
Fig.  10.    Evening.    1       with  Gaule's  quadruple  stain. 

Camera  lucida  drawings,  under  Zeiss,  oc.  8,  obj.  2  mm.,  oil 
I       immersion  (=X  1000  diameters). 
Cerebellum  of  swallows  killed  5  A.M.  and  8  P.M. 
Fig.  13.   Morning.       Corrosive  sublimate,  with  Gaule's  stain. 
Fig.  12.   Evening.    \   Camera  lucida  drawing,  with  Leitz,  j^j  oil  immersion,  obj. 
oc.  3  (=x  965  diameters). 


JoHiiiid  of Morpliolofjij    lb/.  17/. 


PL  viri. 


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Hodge 

A  microscopical  study  of  changes 
due  to  functional  activity  in 
nerve  cells. 


i 


